TY - JOUR AU - Fernández, F. AU - Fernández, A.G. AU - Balo, R. AU - Sánchez-Pedregal, V.M. AU - Royo, M. AU - Soengas, R.G. AU - Estévez, R.J. AU - Estévez, J.C. TI - Polyhydroxylated Cyclopentane β-Amino Acids Derived from d -Mannose and d -Galactose: Synthesis and Protocol for Incorporation into Peptides JF - ACS OMEGA J2 - ACS OMEGA VL - 7 PY - 2022 IS - 2 SP - 2002 EP - 2014 PG - 13 SN - 2470-1343 DO - 10.1021/acsomega.1c05468 UR - https://m2.mtmt.hu/api/publication/32695039 ID - 32695039 AB - A stereoselective synthesis of polyhydroxylated cyclopentane β-amino acids from hexoses is reported. The reaction sequence comprises, as key steps, ring-closing metathesis of a polysubstituted diene intermediate followed by the stereoselective aza-Michael functionalization of the resulting cyclopent-1-ene-1-carboxylic acid ester. Examples of synthesis of polysubstituted 2-aminocyclopentanecarboxylic acid derivatives starting from protected d-mannose and d-galactose are presented. A general protocol for the incorporation of these highly functionalized alicyclic β-amino acids into peptides is also reported. © 2022 The Authors. Published by American Chemical Society. LA - English DB - MTMT ER - TY - JOUR AU - Lee, Yeon Sun TI - Peptidomimetics and Their Applications for Opioid Peptide Drug Discovery JF - BIOMOLECULES J2 - BIOMOLECULES VL - 12 PY - 2022 IS - 9 PG - 40 SN - 2218-273X DO - 10.3390/biom12091241 UR - https://m2.mtmt.hu/api/publication/33167056 ID - 33167056 N1 - Cited By :2 Export Date: 5 September 2023 Correspondence Address: Lee, Y.S.; Department of Pharmacology, United States; email: yeon@email.arizona.edu AB - Despite various advantages, opioid peptides have been limited in their therapeutic uses due to the main drawbacks in metabolic stability, blood-brain barrier permeability, and bioavailability. Therefore, extensive studies have focused on overcoming the problems and optimizing the therapeutic potential. Currently, numerous peptide-based drugs are being marketed thanks to new synthetic strategies for optimizing metabolism and alternative routes of administration. This tutorial review briefly introduces the history and role of natural opioid peptides and highlights the key findings on their structure-activity relationships for the opioid receptors. It discusses details on opioid peptidomimetics applied to develop therapeutic candidates for the treatment of pain from the pharmacological and structural points of view. The main focus is the current status of various mimetic tools and the successful applications summarized in tables and figures. LA - English DB - MTMT ER - TY - JOUR AU - Wtorek, K. AU - Lipiński, P.F.J. AU - Adamska-Bartłomiejczyk, A. AU - Piekielna-Ciesielska, J. AU - Sukiennik, J. AU - Kluczyk, A. AU - Janecka, A. TI - Synthesis, pharmacological evaluation, and computational studies of cyclic opioid peptidomimetics containing β3-lysine JF - MOLECULES J2 - MOLECULES VL - 27 PY - 2022 IS - 1 SN - 1420-3049 DO - 10.3390/molecules27010151 UR - https://m2.mtmt.hu/api/publication/32619226 ID - 32619226 N1 - Department of Biomolecular Chemistry, Medical University of Lodz, Mazowiecka 6/8, Lodz, 92-215, Poland Department of Neuropeptides, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego 5, Warsaw, 02-106, Poland TriMen Chemicals Ltd., Lodz, 92-318, Poland Faculty of Chemistry, University of Wroclaw, Wroclaw, 50-383, Poland Export Date: 26 January 2022 CODEN: MOLEF Correspondence Address: Janecka, A.; Department of Biomolecular Chemistry, Mazowiecka 6/8, Poland; email: anna.janecka@umed.lodz.pl AB - Our formerly described pentapeptide opioid analog Tyr-c[D-Lys-Phe-Phe-Asp]NH2 (desig-nated RP-170), showing high affinity for the mu (MOR) and kappa (KOR) opioid receptors, was much more stable than endomorphine-2 (EM-2) in the rat brain homogenate and displayed remarkable antinociceptive activity after central (intracerebroventricular) and peripheral (intravenous) admin-istration. In this report, we describe the further modification of this analog, which includes the incorporation of a β3-amino acid, (R)-and (S)-β3-Lys, instead of D-Lys in position 2. The influence of such replacement on the biological properties of the obtained analogs, Tyr-c[(R)-β3-Lys-Phe-Phe-Asp]NH2 (RP-171) and Tyr-c[(S)-β3-Lys-Phe-Phe-Asp]NH2, (RP-172), was investigated in vitro. Receptor radiolabeled displacement and functional calcium mobilization assays were performed to measure binding affinity and receptor activation of the new analogs. The obtained data revealed that only one of the diastereoisomeric peptides, RP-171, was able to selectively bind and activate MOR. Molecular modeling (docking and molecular dynamics (MD) simulations) suggests that both compounds should be accommodated in the MOR binding site. However, in the case of the inactive isomer RP-172, fewer hydrogen bonds, as well as instability of the canonical ionic interaction to Asp147, could explain its very low MOR affinity. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. LA - English DB - MTMT ER - TY - JOUR AU - Della, Valle A. AU - Stefanucci, A. AU - Scioli, G. AU - Szűcs, Edina AU - Benyhe, Sándor AU - Pieretti, S. AU - Minosi, P. AU - Sturaro, C. AU - Calò, G. AU - Zengin, G. AU - Mollica, A. TI - Selective MOR activity of DAPEA and Endomorphin-2 analogues containing a (R)-γ-Freidinger lactam in position two JF - BIOORGANIC CHEMISTRY J2 - BIOORG CHEM VL - 115 PY - 2021 PG - 9 SN - 0045-2068 DO - 10.1016/j.bioorg.2021.105219 UR - https://m2.mtmt.hu/api/publication/32334776 ID - 32334776 AB - The use of α-amino-γ lactam of Freidinger (Agl) may serve as an impressive method to increase the biological stability of peptides and an appropriate tool to elucidate their structure-activity relationships. The endomorphin-2 (EM-2) and [D-Ala2, des-Leu5] enkephalin amide (DAPEA) are two linear opioid tetrapeptides agonists of MOR and MOR/DOR respectively. Herein, we investigated the influence of the incorporation of (R/S)-Agl in position 2 and 3 on the biological profile of the aforementioned products in vitro and in vivo. Receptor radiolabeled displacement and functional assays were used to measure in vitro the binding affinity and receptors activation of the novel analogues. The mouse tail flick and formalin tests allowed to observe their antinociceptive effect in vivo. Data revealed that peptide A2D was able to selectively bind and activate MOR with a potent antinociceptive effect after intracerebroventricular (i.c.v.) administration, performing better than the parent compounds EM-2 and DAPEA. Molecular docking calculations helped us to understand the key role exerted by the Freidinger Agl moiety in A2D for the interaction with the MOR binding pocket. © 2021 Elsevier Inc. LA - English DB - MTMT ER - TY - JOUR AU - Tymecka, Dagmara AU - Lipinski, Piotr F. J. AU - Kosson, Piotr AU - Misicka, Aleksandra TI - beta(2)-Homo-Amino Acid Scan of mu-Selective Opioid Tetrapeptide TAPP JF - MOLECULES J2 - MOLECULES VL - 25 PY - 2020 IS - 10 PG - 18 SN - 1420-3049 DO - 10.3390/molecules25102461 UR - https://m2.mtmt.hu/api/publication/31432758 ID - 31432758 N1 - Faculty of Chemistry, University of Warsaw, Pasteura 1, Warsaw, 02-093, Poland Department of Neuropeptides, Mossakowski Medical Research Centre Polish Academy of Sciences, Pawińskiego 5, Warsaw, 02-106, Poland Toxicology Research Laboratory, Mossakowski Medical Research Centre Polish Academy of Sciences, Pawińskiego 5, Warsaw, 02-106, Poland Cited By :4 Export Date: 28 September 2021 CODEN: MOLEF Correspondence Address: Tymecka, D.; Faculty of Chemistry, Pasteura 1, Poland; email: dulok@chem.uw.edu.pl Chemicals/CAS: amino acid, 65072-01-7; aspartic acid, 56-84-8, 6899-03-2; Amino Acids; Aspartic Acid; Ligands; Oligopeptides; Receptors, Opioid, delta; Receptors, Opioid, mu; tyrosyl-alanyl-phenylalanyl-phenylalaninamide Funding details: European Commission, EC, LSHC-CT-2006–037733 Funding details: European Regional Development Fund, FEDER Funding text 1: Funding: The European Union Grant NORMOLIFE (LSHC-CT-2006–037733) supported this work. Funding text 2: Acknowledgments: The calculations were performed at S´wierk Computing Centre, National Centre for Nuclear Research, S´wierk, Poland. Prof. Géza Tóth (Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary) is gratefully acknowledged for providing tritiated radioligands. This work was co-financed by the EU from the European Regional Development Fund under the Operational Programme Innovative Economy, 2007–2013, and with the use of CePT infrastructure financed by the same EU program. AB - TAPP (H-Tyr-d-Ala-Phe-Phe-NH2) is a potent, mu -selective opioid ligand. In order to gain further insights into pharmacophoric features of this tetrapeptide, we have performed a beta (2)-Homo-amino acid (beta (2)hAA) scan of the TAPP sequence. To this aim, 10 novel analogues have been synthesized and evaluated for mu -opioid and delta -opioid receptor affinity as well as for stability in human plasma. The derivatives included compounds in which a (R)- or (S)-beta (2)-Homo-Homologue replaced the amino acids in the TAPP sequence. The derivatives with (R)- or (S)-beta (2)hPhe(4) turned out to bind mu OR with affinities equal to that of the parent. beta (2)hAAs in position 1 and 3 resulted in rather large affinity decreases, but the change differed depending on the stereochemistry. beta (2)-Homologation in the second position gave derivatives with very poor mu OR binding. According to molecular modelling, the presented alpha/beta -peptides adopt a variety of binding poses with their common element being an ionic interaction between a protonable amine of the first residue and Asp147. A feature required for high mu OR affinity seems the ability to accommodate the ring in the fourth residue in a manner similar to that found for TAPP. Contrary to what might be expected, several compounds were significantly less stable in human plasma than the parent compound. LA - English DB - MTMT ER - TY - JOUR AU - Wtorek, Karol AU - Piekielna-Ciesielska, Justyna AU - Janecki, Tomasz AU - Janecka, Anna TI - The search for opioid analgesics with limited tolerance liability JF - PEPTIDES J2 - PEPTIDES VL - 130 PY - 2020 PG - 8 SN - 0196-9781 DO - 10.1016/j.peptides.2020.170331 UR - https://m2.mtmt.hu/api/publication/31335726 ID - 31335726 N1 - Department of Biomolecular Chemistry, Medical University of Lodz, Lodz, Poland Institute of Organic Chemistry, Lodz University of Technology, Lodz, Poland Export Date: 25 July 2020 CODEN: PPTDD Correspondence Address: Janecka, A.; Department of Biomolecular Chemistry, Medical University of Lodz, Mazowiecka 6/8, Poland; email: anna.janecka@umed.lodz.pl LA - English DB - MTMT ER - TY - JOUR AU - Zhao, Long AU - Luo, Keyao AU - Wang, Zhaojuan AU - Wang, Yuan AU - Zhang, Xianghui AU - Yang, Dongxu AU - Ma, Mengtao AU - Zhou, Jingjing AU - Cui, Jiaming AU - Wang, Jing AU - Han, Chao-Zhen-yi AU - Liu, Xin AU - Wang, Rui TI - Design, synthesis, and biological activity of new endomorphin analogs with multi-site modifications JF - BIOORGANIC & MEDICINAL CHEMISTRY J2 - BIOORGAN MED CHEM VL - 28 PY - 2020 IS - 9 PG - 10 SN - 0968-0896 DO - 10.1016/j.bmc.2020.115438 UR - https://m2.mtmt.hu/api/publication/31423916 ID - 31423916 AB - Endomorphin (EM)-1 and EM-2 are the most effective endogenous analgesics with efficient separation of analgesia from the risk of adverse effects. Poor metabolic stability and ineffective analgesia after peripheral administration were detrimental for the use of EMs as novel clinical analgesics. Therefore, here, we aimed to establish new EM analogs via introducing different bifunctional D-amino acids at position 2 of [(2-furyl)Map(4)] EMs. The combination of [(2-furyl)Map4]EMs with D-Arg(2) or D-Cit(2) yielded analogs with enhanced binding affinity to the mu-opioid receptor (MOR) and increased stability against enzymatic degradation (t(1/2) > 300 min). However, the agonistic activities of these analogs toward MOR were slightly reduced. Similar to morphine, peripheral administration of the analog [D-Cit(2), (2-furyl)Map(4)]EM-1 (10) significantly inhibited the pain behavior of mice in multiple pain models. In addition, this EM-1 analog was associated with reduced tolerance, less effect on gastrointestinal mobility, and no significant motor impairment. Compared to natural EMs, the EM analogs synthesized herein had enhanced metabolic stability, bioavailability, and analgesic properties. LA - English DB - MTMT ER - TY - JOUR AU - Wtorek, Karol AU - Artali, Roberto AU - Piekielna-Ciesielska, Justyna AU - Koszuk, Jacek AU - Kluczyk, Alicja AU - Gentilucci, Luca AU - Janecka, Anna TI - Endomorphin-2 analogs containing modified tyrosines: Biological and theoretical investigation of the influence on conformation and pharmacological profile JF - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY J2 - EUR J MED CHEM VL - 179 PY - 2019 SP - 527 EP - 536 PG - 10 SN - 0223-5234 DO - 10.1016/j.ejmech.2019.06.077 UR - https://m2.mtmt.hu/api/publication/30901973 ID - 30901973 N1 - Department of Biomolecular Chemistry, Medical University of Lodz, Mazowiecka 6/8, Lodz, 92-215, Poland Department of Chemistry, University of Bologna, Via Selmi 2, Bologna, 40126, Italy Scientia Advice, di Roberto Artali, Desio, Monza and Brianza 20832, Italy Institute of Organic Chemistry, Lodz University of Technology, Lodz, Poland Faculty of Chemistry, University of Wroclaw, Wroclaw, Poland Cited By :1 Export Date: 12 February 2020 CODEN: EJMCA Correspondence Address: Janecka, A.; Department of Biomolecular Chemistry, Medical University of Lodz, Mazowiecka 6/8, Poland; email: anna.janecka@umed.lodz.pl AB - New analogs of the endogenous opioid agonist endomorphin-2 (EM-2, H-Tyr-Pro-Phe-Phe-NH2) have been obtained by introducing modified tyrosines at the position 1 of the sequence. For all analogs, the cis/trans conformation ratio about the tyramine-Pro amide bond, lipophilicity, receptor affinities, and functional activities, have been determined. Among the novel derivatives, [Dmt(3'-Cl)](EM)-E-1-2 (4) stood out for its subnanomolar mu-opioid receptor affinity and potent agonist activity, superior to that of the parent peptide EM-2. Hybrid quantum mechanics/molecular mechanics docking computations supported the cis tyramine-Pro bioactive conformation, and allowed us to analyze the contribution of the substituents of the "message" tyramine to binding, highlighting the role of halogen-bonding in the higher receptor affinity of peptide 4. (C) 2019 Elsevier Masson SAS. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - De Marco, Rossella AU - Bedini, Andrea AU - Spampinato, Santi AU - Comellini, Lorenzo AU - Zhao, Junwei AU - Artali, Roberto AU - Gentilucci, Luca TI - Constraining Endomorphin-1 by beta,alpha-Hybrid Dipeptide/Heterocycle Scaffolds: Identification of a Novel k-Opioid Receptor Selective Partial Agonist JF - JOURNAL OF MEDICINAL CHEMISTRY J2 - J MED CHEM VL - 61 PY - 2018 IS - 13 SP - 5751 EP - 5757 PG - 7 SN - 0022-2623 DO - 10.1021/acs.jmedchem.8b00296 UR - https://m2.mtmt.hu/api/publication/27602829 ID - 27602829 N1 - Department of Chemistry G. Ciamician, University of Bologna, Via Selmi 2, Bologna, 40126, Italy Department of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 48, Bologna, 40126, Italy Scientia Advice, Desio, Monza and Brianza, 20832, Italy Cited By :14 Export Date: 26 January 2022 CODEN: JMCMA Correspondence Address: Spampinato, S.; Department of Pharmacy and Biotechnology, Via Irnerio 48, Italy; email: santi.spampinato@unibo.it LA - English DB - MTMT ER - TY - JOUR AU - Del Borgo, Mark P AU - Kulkarni, Ketav AU - Aguilar, Marie-Isabel TI - Using β-amino acids and β-peptide templates to create bioactive ligands and biomaterials JF - CURRENT PHARMACEUTICAL DESIGN J2 - CURR PHARM DESIGN VL - 23 PY - 2017 IS - 26 SP - 3772 EP - 3785 PG - 14 SN - 1381-6128 DO - 10.2174/1381612823666170616083031 UR - https://m2.mtmt.hu/api/publication/26919611 ID - 26919611 AB - β-Amino acids are being increasingly used in the design of bioactive ligands and more recently in the generation of novel biomaterials. Peptides containing either individual β-amino acid substitutions or peptides comprised entirely of β-amino acids, display unique properties in terms of their structural and/or chemical characteristics. β Peptides form well-defined secondary structures that exhibit different geometries compared to the corresponding α-peptides. β-Peptides, including α-peptides containing only one or two β-amino acids, can be easily modified with different functional groups and are metabolically stable and, together with the predictable side chain topography, have led to the design of a growing number of bioactive β-peptides with a range of biological targets and therapeutic applications. More recently, our understanding of the folding and self-assembly of β-peptides has resulted in the generation of novel biomaterials. The focus of this review is to examine how the structural and chemical properties of β-peptides have been exploited in the design of bioactive peptides and selfassembled nanomaterials. © 2017 Bentham Science Publishers. LA - English DB - MTMT ER - TY - JOUR AU - De Marco, Rossella AU - Gentilucci, Luca TI - Tryptophan-Containing Non-Cationizable Opioid Peptides - a new chemotype with unusual structure and in vivo activity JF - FUTURE MEDICINAL CHEMISTRY J2 - FUTURE MED CHEM VL - 9 PY - 2017 IS - 17 SP - 2099 EP - 2115 PG - 17 SN - 1756-8919 DO - 10.4155/fmc-2017-0104 UR - https://m2.mtmt.hu/api/publication/27071456 ID - 27071456 N1 - Cited By :3 Export Date: 26 January 2022 Correspondence Address: Gentilucci, L.; Department of Chemistry G Ciamician, via Selmi 2, Italy; email: luca.gentilucci@unibo.it LA - English DB - MTMT ER - TY - JOUR AU - Gach-Janczak, Katarzyna AU - Piekielna-Ciesielska, Justyna AU - Adamska-Bartlomiejczyk, Anna AU - Perlikowska, Renata AU - Kruszynski, Rafal AU - Kluczyk, Alicja AU - Krzywik, Julia AU - Sukiennik, Jaroslaw AU - Cerlesi, Maria Camilla AU - Calo, Girolamo AU - Wasilewski, Andrzej AU - Zielinska, Marta AU - Janecka, Anna TI - Synthesis and activity of opioid peptidomimetics with beta(2)- and beta(3)-amino acids JF - PEPTIDES J2 - PEPTIDES VL - 95 PY - 2017 SP - 116 EP - 123 PG - 8 SN - 0196-9781 DO - 10.1016/j.peptides.2017.07.015 UR - https://m2.mtmt.hu/api/publication/26898077 ID - 26898077 N1 - Department of Biomolecular Chemistry, Medical University, Lodz, Poland Department of X-ray Crystallography and Crystal Chemistry, Institute of General and Ecological Chemistry, Lodz University of Technology, Lodz, Poland Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, Wroclaw, 50-383, Poland TriMen Chemicals Ltd., Lodz, 92-318, Poland Department of Medical Sciences, Section of Pharmacology and Italian Institute of Neuroscience, University of Ferrara, Ferrara, 44121, Italy Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Poland Cited By :4 Export Date: 26 January 2022 CODEN: PPTDD Correspondence Address: Janecka, A.; Department of Biomolecular Chemistry, Poland; email: anna.janecka@umed.lodz.pl LA - English DB - MTMT ER - TY - JOUR AU - Adamska, A AU - Kluczyk, A AU - Cerlesi, MC AU - Calo, G AU - Janecka, A AU - Borics, Attila TI - Synthesis, biological evaluation and structural analysis of novel peripherally active morphiceptin analogs JF - BIOORGANIC & MEDICINAL CHEMISTRY J2 - BIOORGAN MED CHEM VL - 24 PY - 2016 IS - 7 SP - 1582 EP - 1588 PG - 7 SN - 0968-0896 DO - 10.1016/j.bmc.2016.02.034 UR - https://m2.mtmt.hu/api/publication/3029039 ID - 3029039 LA - English DB - MTMT ER - TY - JOUR AU - Fraczak, Oliwia AU - Lasota, Anika AU - Kosson, Piotr AU - Lesniak, Anna AU - Muchowska, Adriana AU - Lipkowski, Andrzej W AU - Olma, Aleksandra TI - Biphalin analogs containing beta(3)-homo-amino acids at the 4,4 ' positions: Synthesis and opioid activity profiles JF - PEPTIDES J2 - PEPTIDES VL - 66 PY - 2015 SP - 13 EP - 18 PG - 6 SN - 0196-9781 DO - 10.1016/j.peptides.2015.02.004 UR - https://m2.mtmt.hu/api/publication/25383078 ID - 25383078 LA - English DB - MTMT ER - TY - JOUR AU - Hu, Miao AU - Giulianotti, Marc A AU - McLaughlin, Jay P AU - Shao, Jiaan AU - Debevec, Ginamarie AU - Maida, Laura E AU - Geer, Phaedra AU - Cazares, Margaret AU - Misler, Jaime AU - Li, Ling AU - Dooley, Colette AU - Ganno, Michelle L AU - Eans, Shainnel O AU - Mizrachi, Elisa AU - Santos, Radleigh G AU - Yongye, Austin B AU - Houghten, Richard A AU - Yu, Yongping TI - Synthesis and biological evaluations of novel endomorphin analogues containing alpha-hydroxy-beta-phenylalanine (AHPBA) displaying mixed mu/delta opioid receptor agonist and delta opioid receptor antagonist activities JF - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY J2 - EUR J MED CHEM VL - 92 PY - 2015 SP - 270 EP - 281 PG - 12 SN - 0223-5234 DO - 10.1016/j.ejmech.2014.12.049 UR - https://m2.mtmt.hu/api/publication/25791119 ID - 25791119 N1 - Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, United States Cited By :16 Export Date: 8 September 2023 CODEN: EJMCA Correspondence Address: Houghten, R.A.; Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, United States LA - English DB - MTMT ER - TY - CHAP AU - Mollica, A. AU - Stefanucci, A. AU - Costante, R. AU - Hruby, V.J. ED - Atta-ur, Rahman TI - Rational approach to the design of bioactive peptidomimetics: Recent developments in opioid agonist peptides T2 - Studies in Natural Products Chemistry VL - 46 PB - Elsevier B.V. CY - Amsterdam SN - 9780444634627 T3 - Studies in Natural Products Chemistry, ISSN 1572-5995 ; 46. PY - 2015 SP - 27 EP - 68 PG - 42 DO - 10.1016/B978-0-444-63462-7.00002-6 UR - https://m2.mtmt.hu/api/publication/30332200 ID - 30332200 N1 - \n Dipartimento di Farmacia, Università di Chieti-Pescara G. d'Annunzio, Chieti, Italy \n Dipartimento di Chimica, Sapienza, Università di Roma, Rome, Italy \n Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, United States \n Cited By :5 \n Export Date: 28 November 2018 \n Correspondence Address: Mollica, A.; Dipartimento di Farmacia, Università di Chieti-Pescara G. d'AnnunzioItaly AB - Pharmacological management of severe and chronic pain remains a difficult achievement with currently available analgesic drugs. The design and development of potent opioid analogs with reduced tolerance, dependence, respiratory depression, and other unwanted side effects, could be of great value in the clinical treatment of chronic pain. The hierarchical approach to peptidomimetic design has dramatically advanced over the past three decades; a significant target in research since the discovery of multiple opioid receptors has been to develop highly potent and selective opioid receptor peptidomimetics that overcome the problems related to scarce bioavailability, enzymatic degradation, and low safety profile of natural peptides. Peptide drug design is a high multidisciplinary area that often relies on the state-of-the-art of organic chemistry, pharmacology, and biochemistry, computational methods and biophysical methods for determining the structural, conformational, topographical, and dynamic properties of designed ligands. With the aim to explore the recent advancements in opioids research, in this chapter, particular attention has been paid on the structural modifications of natural opioid peptides to obtain potent, selective, and stable opioid agonists. In addition, we focused our attention on μ/δ mixed agonists and novel approaches based on multitarget ligands, as discussed in section "Future Perspectives and Conclusions." © 2015 Elsevier B.V. LA - English DB - MTMT ER - TY - JOUR AU - Cabrele, C AU - Martinek, Tamás AU - Reiser, O AU - Berlicki, Ł TI - Peptides containing β-amino acid patterns: Challenges and successes in medicinal chemistry JF - JOURNAL OF MEDICINAL CHEMISTRY J2 - J MED CHEM VL - 57 PY - 2014 IS - 23 SP - 9718 EP - 9739 PG - 22 SN - 0022-2623 DO - 10.1021/jm5010896 UR - https://m2.mtmt.hu/api/publication/2817673 ID - 2817673 AB - The construction of bioactive peptides using β-amino acid-containing sequence patterns is a very promising strategy to obtain analogues that exhibit properties of high interest for medicinal chemistry applications. β-Amino acids have been shown to modulate the conformation, dynamics, and proteolytic susceptibility of native peptides. They can be either combined with α-amino acids by following specific patterns, which results in backbone architectures with well-defined orientations of the side chain functional groups, or assembled in de novo-designed bioactive β- or α,β-peptidic sequences. Such peptides display various biological functions, including antimicrobial activity, inhibition of protein-protein interactions, agonism/antagonism of GPCR ligands, and anti-angiogenic activity. LA - English DB - MTMT ER - TY - JOUR AU - Ilisz, István AU - Grecsó, Nóra AU - Aranyi, Anita AU - Suchotin, P AU - Tymecka, D AU - Wilenska, B AU - Misicka, A AU - Fülöp, Ferenc AU - Lindner, W AU - Péter, Antal TI - Enantioseparation of β2-amino acids on cinchona alkaloid-based zwitterionic chiral stationary phases. Structural and temperature effects JF - JOURNAL OF CHROMATOGRAPHY A J2 - J CHROMATOGR A VL - 1334 PY - 2014 SP - 44 EP - 54 PG - 11 SN - 0021-9673 DO - 10.1016/j.chroma.2014.01.075 UR - https://m2.mtmt.hu/api/publication/2547618 ID - 2547618 N1 - Funding Agency and Grant Number: Hungarian National Science Foundation [OM K 108847, TeT-10-1-2011-0055]; Pilar Franco (Chiral Technologies Europe); TAMOP [4.2.4. A/2-11-1-2012-0001]; European Union; European Social Fund; European Regional Development Fund under the Operational Program Innovative Economy Funding text: This work was supported by Hungarian National Science Foundation grant OM K 108847 and TeT-10-1-2011-0055. The support of Pilar Franco (Chiral Technologies Europe) in providing of Chiralpak columns is gratefully acknowledged. The research of N.G. was realized in the frames of TAMOP 4.2.4. A/2-11-1-2012-0001 "National Excellence Program - Elaborating and operating an inland student and researcher personal support system convergence program. The project was subsidized by the European Union and co-financed by the European Social Fund". "The study was carried out at the Biological and Chemical Research Center, University of Warsaw, established within the project co-financed by EU from the European Regional Development Fund under the Operational Program Innovative Economy, 2007-2013, and with the use of CeePT infrastructure financed by the same EU programme". AB - The enantiomers of sixteen unusual β2-amino acids were directly separated on chiral stationary phases containing quinine- or quinidine-based zwitterionic selectors. The effects of the mobile phase composition, the structure of the analyte and temperature on the separations were investigated. Experiments were performed at constant mobile phase compositions in the temperature range -5 to 55°C in order to study the effects of temperature, and thermodynamic parameters were estimated from plots of lnk or lnα vs. 1/T. Some mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes. It was found that the enantiomeric separations were in most cases enthalpically driven, but entropically driven separation was also observed. The sequence of elution of the enantiomers was determined in some cases. © 2014 Elsevier B.V. LA - English DB - MTMT ER - TY - THES AU - Airaghi, Francesco TI - SYNTHESIS, STRUCTURAL INVESTIGATION AND BIOLOGICAL EVALUATION OF CONFORMATIONALLY CONSTRAINED PEPTIDOMIMETICS PB - University of Milano PY - 2013 SP - 211 UR - https://m2.mtmt.hu/api/publication/30615868 ID - 30615868 AB - This Ph.D. thesis is located in the medicinal chemistry research field. Peptides are among the most studied entities as potential drug candidates, due to their natural abundance and biological implications. However, as drugs they possess several disadvantages because of low bioavailability and short half-life. Peptidomimetics try to overcome such drawbacks, maintaining meanwhile the biological activity. These mimics can also be useful to define bioactive forms of natural peptides, for instance through insertion of conformational constrictions able to reduce the peptide inherent flexibility. Thus, I explored the synthesis and the evaluation of some conformationally constrained peptidomimetics which potentially could be employed into different scientific fields and pharmaceutical contexts. Once prepared these scaffolds, I evaluated their secondary structure by means of spectroscopic methods including NMR and IR techniques. After insertion into more complex structures, strictly related to biologically active compounds, I verified their therapeutic potential. In some cases I could achieve very interesting biological results, in the range of activity of the natural corresponding peptides or of the reference lead compounds. I also tried to rationalize the biological activity outcomes, by joining them with molecular mechanics and docking-based structural investigation. LA - English DB - MTMT ER - TY - JOUR AU - Lesma, G AU - Salvadori, S AU - Airaghi, F AU - Murray, TF AU - Recca, T AU - Sacchetti, A AU - Balboni, G AU - Silvani, A TI - Structural and Biological Exploration of Phe(3)-Phe(4)-Modified Endomorphin-2 Peptidomimetics JF - ACS MEDICINAL CHEMISTRY LETTERS J2 - ACS MED CHEM LETT VL - 4 PY - 2013 IS - 8 SP - 795 EP - 799 PG - 5 SN - 1948-5875 DO - 10.1021/ml400189r UR - https://m2.mtmt.hu/api/publication/23594314 ID - 23594314 N1 - Megjegyzés-23457018 FN: Thomson Reuters Web of Knowledge Megjegyzés-23460720 FN: Thomson Reuters Web of Knowledge Megjegyzés-23469098 FN: Thomson Reuters Web of Knowledge Megjegyzés-23469175 FN: Thomson Reuters Web of Knowledge Megjegyzés-23451742 FN: Thomson Reuters Web of Knowledge LA - English DB - MTMT ER - TY - JOUR AU - Lesma, G AU - Salvadori, S AU - Airaghi, F AU - Bojnik, Engin AU - Borsodi, Anna AU - Recca, T AU - Sacchetti, A AU - Balboni, G AU - Silvani, A TI - Synthesis, pharmacological evaluation and conformational investigation of endomorphin-2 hybrid analogues JF - MOLECULAR DIVERSITY J2 - MOL DIVERS VL - 17 PY - 2013 IS - 1 SP - 19 EP - 31 PG - 13 SN - 1381-1991 DO - 10.1007/s11030-012-9399-5 UR - https://m2.mtmt.hu/api/publication/2208938 ID - 2208938 AB - This study reports on new pharmacologically active endomorphin-2 analogues, incorporating β 2-hPhe, β 3-hPhe and β 3-hTic unnatural amino acids in the place of the Phe 3-Phe 4residues. Such α, β-hybrid analogues were designed to exploit the great potential of β-amino acids in generating conformational variation at the key positions 3 and 4, with the aim of evaluating the effect on the opioid binding affinity. Ligand-stimulated binding assays indicated that some analogues retained a significant affinity, especially for the δ receptor. 1H NMR and molecular modelling suggested the predominance of bent structures for all compounds. The molecular docking with the μ-opioid receptor model was also performed, highlighting a common binding mode for active compounds and helping to rationalize the observed structure-activity data. © 2012 Springer Science+Business Media Dordrecht. LA - English DB - MTMT ER - TY - JOUR AU - Liu, X AU - Wang, Y AU - Xing, YH AU - Yu, J AU - Ji, H AU - Kai, M AU - Wang, ZL AU - Wang, D AU - Zhang, YX AU - Zhao, DP AU - Wang, R TI - Design, Synthesis, and Pharmacological Characterization of Novel Endomorphin-1 Analogues as Extremely Potent mu-Opioid Agonists JF - JOURNAL OF MEDICINAL CHEMISTRY J2 - J MED CHEM VL - 56 PY - 2013 IS - 7 SP - 3102 EP - 3114 PG - 13 SN - 0022-2623 DO - 10.1021/jm400195y UR - https://m2.mtmt.hu/api/publication/24536999 ID - 24536999 N1 - Megjegyzés-23457876 FN: Thomson Reuters Web of Knowledge Cited By :32 Export Date: 24 September 2021 CODEN: JMCMA Correspondence Address: Wang, R.; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, , Lanzhou 730000, China; email: wangrui@lzu.edu.cn LA - English DB - MTMT ER - TY - JOUR AU - Muranyi, M AU - Cinar, Resat AU - Kékesi, Orsolya Sára AU - Birkás, Erika AU - Fábián, Gabriella AU - Bozó, Bea AU - Zentai, A AU - Tóth, Géza AU - Kicsi, EG AU - Macsai, M AU - Dochnal, Roberta AU - Szabó, Gyula AU - Szűcs, Mária TI - Ligand-Specific Regulation of the Endogenous Mu-Opioid Receptor by Chronic Treatment with Mu-Opioid Peptide Agonists JF - BIOMED RESEARCH INTERNATIONAL J2 - BIOMED RES INT VL - 2013 PY - 2013 PG - 9 SN - 2314-6133 DO - 10.1155/2013/501086 UR - https://m2.mtmt.hu/api/publication/2486869 ID - 2486869 AB - Since the discovery of the endomorphins (EM), the postulated endogenous peptide agonists of the mu-opioid receptors, several analogues have been synthesized to improve their binding and pharmacological profiles. We have shown previously that a new analogue, cis-1S,2R-aminocyclohexanecarboxylic acid(2)-endomorphin-2 (ACHC-EM2), had elevated mu-receptor affinity, selectivity, and proteolytic stability over the parent compound. In the present work, we have studied its antinociceptive effects and receptor regulatory processes. ACHC-EM2 displayed a somewhat higher (60%) acute antinociceptive response than the parent peptide, EM2 (45%), which peaked at 10 min after intracerebroventricular (icv) administration in the rat tail-flick test. Analgesic tolerance developed to the antinociceptive effect of ACHC-EM2 upon its repeated icv injection that was complete by a 10-day treatment. This was accompanied by attenuated coupling of mu-sites to G-proteins in subcellular fractions of rat brain. Also, the density of mu-receptors was upregulated by about 40% in the light membrane fraction, with no detectable changes in surface binding. Distinct receptor regulatory processes were noted in subcellular fractions of rat brains made tolerant by the prototypic full mu-agonist peptide, DAMGO, and its chloromethyl ketone derivative, DAMCK. These results are discussed in light of the recently discovered phenomenon, that is, the "so-called biased agonism" or "functional selectivity". LA - English DB - MTMT ER - TY - JOUR AU - Palkó, Márta AU - Hanninen, MM AU - Sillanpaa, R AU - Fülöp, Ferenc TI - Syntheses of four enantiomers of 2,3-diendo- and 3-endo-aminobicyclo[2.2.2] oct-5-ene-2-exo-carboxylic acid and their saturated analogues JF - MOLECULES J2 - MOLECULES VL - 18 PY - 2013 IS - 12 SP - 15080 EP - 15093 PG - 14 SN - 1420-3049 DO - 10.3390/molecules181215080 UR - https://m2.mtmt.hu/api/publication/2489391 ID - 2489391 N1 - Institute of Pharmaceutical Chemistry, University of Szeged, Eotvos utca 6, Szeged H-6720, Hungary Department of Chemistry, University of Jyvaskyla, Turku FIN-40014, Finland Stereochemistry Research Group of the Hungarian Academy of Sciences, University of Szeged, Eotvos utca 6, Szeged H-6720, Hungary Cited By :5 Export Date: 20 June 2023 CODEN: MOLEF Correspondence Address: Fulop, F.; Institute of Pharmaceutical Chemistry, Eotvos utca 6, Szeged H-6720, Hungary; email: fulop@pharm.u-szeged.hu Chemicals/CAS: Carboxylic Acids; Esters LA - English DB - MTMT ER - TY - JOUR AU - Varamini, P AU - Blanchfield, JT AU - Tóth, István TI - Endomorphin Derivatives with Improved Pharmacological Properties JF - CURRENT MEDICINAL CHEMISTRY J2 - CURR MED CHEM VL - 20 PY - 2013 IS - 22 SP - 2741 EP - 2758 PG - 18 SN - 0929-8673 DO - 10.2174/0929867311320220002 UR - https://m2.mtmt.hu/api/publication/2877333 ID - 2877333 LA - English DB - MTMT ER - TY - JOUR AU - Borics, Attila AU - Mallareddy, Jayapelreddy AU - Timári, István AU - E Kövér, Katalin AU - Keresztes, Attila AU - Tóth, Géza TI - The Effect of Pro(2) Modifications on the Structural and Pharmacological Properties of Endomorphin-2. JF - JOURNAL OF MEDICINAL CHEMISTRY J2 - J MED CHEM VL - 55 PY - 2012 IS - 19 SP - 8418 EP - 8428 PG - 11 SN - 0022-2623 DO - 10.1021/jm300836n UR - https://m2.mtmt.hu/api/publication/2085025 ID - 2085025 AB - Endomorphins (EM-1 and EM-2) are selective, high affinity agonists of the mu-opioid (MOP) receptor, an important target in pain regulation. Their clinical use is impeded by their poor metabolic stability and limited entry to the central nervous system. In this study, the Pro(2) residue of EM-2 was modified systematically through substitution by hydroxyproline (Hyp), (S)-beta-homoproline (betaPro), 2-aminocyclopentene-1-carboxylic acid (DeltaAcpc), or 2-aminocyclohexene-1-carboxylic acid (DeltaAchc) to obtain stable MOP active compounds. Both Hyp(2) and betaPro(2) substitution decreased receptor affinity. Analogues incorporating alicyclic beta-amino acids exhibited diverse receptor binding properties, depending on the configuration of the substituent side-chain. (1S,2R)DeltaAcpc(2)-EM-2 was shown to have MOP affinity and selectivity comparable to those of EM-2 and proved to act as agonist while being resistant to proteolysis. NMR and molecular dynamics (MD) studies revealed that bent backbone structures are predominant in the most potent analogues, while their presence is less pronounced in ligands of lower receptor affinity. LA - English DB - MTMT ER - TY - JOUR AU - Kovács, Gyula István AU - Petrovszki, Zita AU - Mallareddy, Jayapelreddy AU - Tóth, Géza AU - Benedek, György AU - Horváth, Gyöngyi TI - Characterization of antinociceptive potency of endomorphin-2 derivatives with unnatural amino acids in rats JF - ACTA PHYSIOLOGICA HUNGARICA J2 - ACTA PHYSIOL HUNG VL - 99 PY - 2012 IS - 3 SP - 353 EP - 363 PG - 11 SN - 0231-424X DO - 10.1556/APhysiol.99.2012.3.12 UR - https://m2.mtmt.hu/api/publication/2057815 ID - 2057815 LA - English DB - MTMT ER - TY - JOUR AU - Liu, Wei X AU - Wang, Rui TI - Endomorphins: potential roles and therapeutic indications in the development of opioid peptide analgesic drugs JF - MEDICINAL RESEARCH REVIEWS J2 - MED RES REV VL - 32 PY - 2012 IS - 3 SP - 536 EP - 580 PG - 45 SN - 0198-6325 DO - 10.1002/med.20222 UR - https://m2.mtmt.hu/api/publication/25394995 ID - 25394995 N1 - Cited By :70 Export Date: 4 February 2024 CODEN: MRRED LA - English DB - MTMT ER - TY - JOUR AU - Mallareddy, Jayapelreddy AU - Tóth, Géza AU - Fazakas, Csilla AU - Molnár, Judit AU - Nagyőszi, Péter AU - Lipkowski, AW AU - Krizbai, István Adorján AU - Wilhelm, Imola Mária TI - Transport Characteristics of Endomorphin-2 Analogues in Brain Capillary Endothelial Cells. JF - CHEMICAL BIOLOGY & DRUG DESIGN J2 - CHEM BIOL DRUG DES VL - 79 PY - 2012 IS - 4 SP - 507 EP - 513 PG - 7 SN - 1747-0277 DO - 10.1111/j.1747-0285.2011.01306.x UR - https://m2.mtmt.hu/api/publication/1921998 ID - 1921998 AB - Due to their poor metabolic stability and limited blood-brain barrier (BBB) permeability, endomorphins (EMs) have a low analgesic efficacy when administered systemically. Therefore, it is of great importance to design analogues with improved peptidase resistance and better delivery to the central nervous system. Recently, novel endomorphin-2 (EM-2) analogues have been synthesized, which proved to bind with high affinity and selectivity to the mu-opioid receptors, and showed proteolytic resistance. In this study we have analyzed the transport characteristics of EM-2 and three of its analogues (Dmt-Pro-Phe-Phe-NH(2) , Tyr-(1S,2R)Acpc-Phe-Phe-NH(2) and Tyr-(1S,2R)Achc-Phe-Phe-NH(2) ) using an in vitro BBB model. The lipohilicity of the analogues, as assessed by their octanol/water partition coefficients, was higher than that of EM-2. The flux of all four peptides from the apical (blood) side to the basolateral (brain) side was not saturable in the 10 nM to 1 mM concentration range, suggesting that a passive mechanism plays a major role in their transport. The permeability coefficient of the analogues was significantly higher than that of EM-2, suggesting increased BBB penetration properties. We conclude that due to their good peptidase resistance and improved transport through brain endothelial cells these EM-2 analogues will have better analgesic properties in vivo. (c) 2011 John Wiley & Sons A/S. LA - English DB - MTMT ER - TY - JOUR AU - Németh, Krisztina AU - Mallareddy, Jayapelreddy AU - Domonkos, Celesztina Diána AU - Benéné Visy, Júlia AU - Tóth, Géza AU - Péter, Antal TI - Stereoselective analysis of endomorphin diastereomers: Resolution of biologically active analogues by capillary electrophoresis applying cyclodextrins as mobile phase additives. JF - JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS J2 - J PHARMACEUT BIOMED ANAL VL - 70 PY - 2012 SP - 32 EP - 39 PG - 8 SN - 0731-7085 DO - 10.1016/j.jpba.2012.05.013 UR - https://m2.mtmt.hu/api/publication/2057724 ID - 2057724 AB - Seven diastereomer pairs of tetrapeptide analogues (TP) of endomorphin-1 and -2 were synthesized. A stereoselective capillary electrophoretic method was developed for controlling stereoisomeric ratio or purity. The isoelectric points of the tetrapeptides were between 8.3 and 8.9 as predicted and measured. A few of the analytes could be resolved without selectors due to the difference in their mobility. Neutral and anionic cyclodextrins (CDs) were applied in order to improve resolution. Stability constants as well as the mobilities of complexes were determined. Contributions of differences in the mobilities of free analytes and in the mobilities and stabilities of their complexes formed by CDs were equally important in the efficient resolution and migration order of diastereomers. As a result of the optimization of the pH of buffers and the concentration of the CD derivatives each diastereomer pair was resolved at baseline at least or better. LA - English DB - MTMT ER - TY - JOUR AU - Ötvös, Sándor Balázs AU - Mándity, István AU - Fülöp, Ferenc TI - Highly Efficient 1,4-Addition of Aldehydes to Nitroolefins: Organocatalysis in Continuous Flow by Solid-Supported Peptidic Catalysts JF - CHEMSUSCHEM J2 - CHEMSUSCHEM VL - 5 PY - 2012 IS - 2 SP - 266 EP - 269 PG - 4 SN - 1864-5631 DO - 10.1002/cssc.201100332 UR - https://m2.mtmt.hu/api/publication/1955479 ID - 1955479 N1 - WC: Chemistry, Multidisciplinary LA - English DB - MTMT ER - TY - JOUR AU - Podwysocka, D AU - Kosson, P AU - Lipkowski, AW AU - Olma, A TI - TAPP analogs containing beta(3)-homo-amino acids: synthesis and receptor binding JF - JOURNAL OF PEPTIDE SCIENCE J2 - J PEPT SCI VL - 18 PY - 2012 IS - 9 SP - 556 EP - 559 PG - 4 SN - 1075-2617 DO - 10.1002/psc.2433 UR - https://m2.mtmt.hu/api/publication/23457877 ID - 23457877 LA - English DB - MTMT ER - TY - JOUR AU - Saavedra, CJ AU - Boto, A AU - Hernández, R AU - Miranda, JI AU - Aizpurua, JM TI - Conformation and chiral effects in α,β,α-tripeptides JF - JOURNAL OF ORGANIC CHEMISTRY J2 - J ORG CHEM VL - 77 PY - 2012 IS - 14 SP - 5907 EP - 5913 PG - 7 SN - 0022-3263 DO - 10.1021/jo300892u UR - https://m2.mtmt.hu/api/publication/22489896 ID - 22489896 LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Géza AU - Mallareddy, Jayapelreddy AU - Tóth, Fanni AU - Lipkowski, AW AU - Tourwe, D TI - Radiotracers, tritium labelling of neuropeptides JF - ARKIVOC J2 - ARKIVOC VL - 2012 PY - 2012 SP - 163 EP - 174 PG - 12 SN - 1551-7012 DO - 10.3998/ark.5550190.0013.515 UR - https://m2.mtmt.hu/api/publication/2057817 ID - 2057817 N1 - Megjegyzés-23433468 PN 5 WoS:hiba:000308697400015 2019-03-03 19:47 kötet nem egyezik LA - English DB - MTMT ER - TY - JOUR AU - Wang, Y AU - Xing, YH AU - Liu, X AU - Ji, H AU - Kai, M AU - Chen, ZY AU - Yu, J AU - Zhao, DP AU - Ren, H AU - Wang, R TI - A New Class of Highly Potent and Selective Endomorphin-1 Analogues Containing alpha-Methylene-beta-aminopropanoic Acids (Map) JF - JOURNAL OF MEDICINAL CHEMISTRY J2 - J MED CHEM VL - 55 PY - 2012 IS - 13 SP - 6224 EP - 6236 PG - 13 SN - 0022-2623 DO - 10.1021/jm300664y UR - https://m2.mtmt.hu/api/publication/24537009 ID - 24537009 N1 - Cited By :38 Export Date: 24 September 2021 CODEN: JMCMA Correspondence Address: Wang, R.; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, , Lanzhou, 730000, China; email: wangrui@lzu.edu.cn LA - English DB - MTMT ER - TY - JOUR AU - Keresztes, Attila AU - Birkás, Erika AU - Pahi, A AU - Tóth, Géza AU - Bakota, L AU - Gulya, Károly AU - Szűcs, Mária TI - Pharmacology of a new tritiated endomorphin-2 analog containing the proline mimetic cis-2-aminocyclohexanecarboxylic acid JF - PEPTIDES J2 - PEPTIDES VL - 32 PY - 2011 IS - 4 SP - 722 EP - 728 PG - 7 SN - 0196-9781 DO - 10.1016/j.peptides.2011.01.017 UR - https://m2.mtmt.hu/api/publication/1868184 ID - 1868184 AB - As part of ongoing work aimed at generating proteolytically stable, readily applicable, radiolabeled endomorphin-2 (EM-2) analogs for elucidation of the topological requirements of peptide binding to mu-opioid receptors, we report here on the synthesis, radiolabeling, binding kinetics and binding site distribution of an EM-2 analog in which Pro(2) is replaced by 2-aminocyclohexanecarboxylic acid, ACHC. [H-3][(1S,2R)ACHC](EM)-E-2-2 (specific activity 63.49 Ci x mmol(-1)) bound specifically to its binding sites with high affinity (K-D = 0.55 +/- 0.06 nM) and saturably, yielding a receptor density, B-max of 151 +/- 4 fmol x mg protein(-1) in rat brain membranes. A similar affinity value was obtained in kinetic assays. Both Na+ and Gpp(NH)p decreased the affinity, proving the agonist character of the radioligand. Specific mu-opioid ligands displaced the radioligand with much higher affinities than did delta- and kappa-ligands. The autoradiographic distribution of the binding sites of [H-3][(1S,2R)ACHC](EM)-E-2-2 agreed well with the known locations of the mu-opioid receptors in the rat brain. In consequence of its high affinity, selectivity and enzymatic resistance [19], the new radioligand will be a good tool in studies of the topographical requirements of mu-opioid-specific peptide binding. (C) 2011 Elsevier Inc. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Mallareddy, Jayapelreddy AU - Borics, Attila AU - Keresztes, Attila AU - E Kövér, Katalin AU - Tourwe, D AU - Tóth, Géza TI - Design, Synthesis, Pharmacological Evaluation, and Structure-Activity Study of Novel Endomorphin Analogues with Multiple Structural Modifications JF - JOURNAL OF MEDICINAL CHEMISTRY J2 - J MED CHEM VL - 54 PY - 2011 IS - 5 SP - 1462 EP - 1472 PG - 11 SN - 0022-2623 DO - 10.1021/jm101515v UR - https://m2.mtmt.hu/api/publication/1921580 ID - 1921580 AB - This study reports on new proteolytically stable, pharmacologically active endomorphin analogues, incorporating Dmt(1), Achc(2), pFPhe(4), or beta MePhe(4) unnatural amino acids. Consistent with earlier results, it was found that the analogues carrying anti and Achc2 residues displayed the highest p-opioid receptor affinities, depending upon the configuration of the incorporated Achc(2). Combination of such derivatives with pFPhe(4) or beta MePhe(4) yielded further compounds with variable binding potencies. Combined application of Dmt(1), cis-(1S,2R)Achc(2), and pFPhe(4) (compound 16) resulted in the most potent analogue. Ligand stimulated [S-35]GTP gamma S binding assays indicated that the analogues retained their agonist activities and opioid receptor specificities. NMR and molecular modeling studies of the analogues containing beta MePhe(4) or pFPhe(4) confirmed the predominance of bent structures, however, it is apparent that bent structures are energetically more favored than random/extended structures for all studied compounds. LA - English DB - MTMT ER - TY - JOUR AU - Szilágyi, László AU - E Kövér, Katalin AU - Batta, Gyula AU - Bányai, István AU - Tóth, Imre TI - Az NMR spektroszkópia 40 éve Debrecenben. 40 years of NMR at the Department of Chemistry, University of Debrecen TS - 40 years of NMR at the Department of Chemistry, University of Debrecen JF - MAGYAR KÉMIAI FOLYÓIRAT - KÉMIAI KÖZLEMÉNYEK (1997-) J2 - MAGY KÉM FOLY KÉM KÖZL VL - 117 PY - 2011 IS - 2-3 SP - 133 EP - 141 PG - 9 SN - 1418-9933 UR - https://m2.mtmt.hu/api/publication/1761918 ID - 1761918 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Vandormael, B AU - De Wachter, R AU - Martins, JC AU - Hendrickx, PMS AU - Keresztes, Attila AU - Ballet, S AU - Mallareddy, Jayapelreddy AU - Tóth, Fanni AU - Tóth, Géza AU - Tourwe, D TI - Asymmetric Synthesis and Conformational Analysis by NMR Spectroscopy and MD of Aba- and alpha-MeAba-Containing Dermorphin Analogues JF - CHEMMEDCHEM J2 - CHEMMEDCHEM VL - 6 PY - 2011 IS - 11 SP - 2035 EP - 2047 PG - 13 SN - 1860-7179 DO - 10.1002/cmdc.201100314 UR - https://m2.mtmt.hu/api/publication/1921985 ID - 1921985 N1 - Megjegyzés-21825048 : FN Thomson Reuters Web of Knowledge WC: Chemistry, Medicinal; Pharmacology & Pharmacy Megjegyzés-22126478 DI: 10.1002/cmdc.201100314 AB - Dermorphin analogues, containing a (S)- and (R)-4-amino1,2,4,5-tetrahydro-2-benzazepin-3-one scaffold (Aba) and the alpha-methylated analogues as conformationally constrained phenylalanines, were prepared. Asymmetric phase-transfer catalysis was unable to provide the (S)-alpha-Me-o-cyanophenylalanine precursor for (S)-alpha-MeAba in acceptable enantiomeric purity. However, by using a Schollkopf chiral auxiliary, this intermediate was obtained in 88% ee. [(S)-Aba 3-Gly 4] dermorphin retained mu-opioid affinity but displayed an increased delta-affinity. The corresponding R epimer was considerably less potent. In contrast, the [(R)-alpha-MeAba3-Gly4] dermorphin isomer was more potent than its S epimer. Tar-MD simulations of both non-methylated [Aba 3-Gly 4] dermorphin analogues showed a degree of folding at the C-terminal residues toward the N terminus of the peptide, without however, adopting a stabilized beta-turn conformation. The alpha-methylated analogues, on the other hand, exhibited a type I/I' beta-turn conformation over the alpha-MeAba3 and Gly4 residues, which was stabilized by a hydrogen bond involving Tyr5-H(N) and D-Ala 2-CO. LA - English DB - MTMT ER - TY - JOUR AU - Borics, Attila AU - Tóth, Géza TI - Structural comparison of mu-opioid receptor selective peptides confirmed four parameters of bioactivity JF - JOURNAL OF MOLECULAR GRAPHICS AND MODELLING J2 - J MOL GRAPH MODEL VL - 28 PY - 2010 IS - 6 SP - 495 EP - 505 PG - 11 SN - 1093-3263 DO - 10.1016/j.jmgm.2009.11.006 UR - https://m2.mtmt.hu/api/publication/1921000 ID - 1921000 N1 - Megjegyzés-22126479 DI: 10.1016/j.jmgm.2009.11.006 Megjegyzés-22189227 DI: 10.1016/j.jmgm.2009.11.006 Megjegyzés-22194324 DI: 10.1016/j.jmgm.2009.11.006 Megjegyzés-22209514 DI: 10.1016/j.jmgm.2009.11.006 Megjegyzés-22217972 DI: 10.1016/j.jmgm.2009.11.006 Megjegyzés-23083039 DI: 10.1016/j.jmgm.2009.11.006 AB - Structural determinants of binding to the mu-opioid receptor, an important target in analgesia, attract great scientific attention. Many natural and synthetic peptides and peptidomimetics were shown previously to bind to this receptor selectively but there is no consensus about the structure responsible for biological activity. No high resolution structure of this receptor is available and the binding site of ligands is not exactly known. However, mu-opioid ligands with similar affinity and selectivity should possess at least one common structural feature. Comparative structural analysis of such ligands, considering adequate representation of binding conditions, may reveal key features of bioactivity. In this study ten mu-opioid receptor ligands, DAMGC, Tyr-W-MIF-1, morphiceptin, endomorphin-1 and 2 and their analogues, possessing different affinity and selectivity, were examined using molecular dynamics. Conformational preference of these molecules was determined in H2O and DMSO along with structural properties previously proposed to be important for binding. Four of such structural requirements were confirmed to be important, providing a possible structural model of receptor binding. Simultaneous fulfillment of these requirements results most likely in high affinity binding to the mu-opioid receptor. (C) 2009 Elsevier Inc. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Keresztes, Attila AU - Borics, Attila AU - Tóth, Géza TI - Recent advances in endomorphin engineering JF - CHEMMEDCHEM J2 - CHEMMEDCHEM VL - 5 PY - 2010 IS - 8 SP - 1176 EP - 1196 PG - 21 SN - 1860-7179 DO - 10.1002/cmdc.201000077 UR - https://m2.mtmt.hu/api/publication/1921178 ID - 1921178 N1 - Megjegyzés-22145409 DI: 10.1002/cmdc.201000077 Megjegyzés-22152739 DI: 10.1002/cmdc.201000077 Megjegyzés-22161204 DI: 10.1002/cmdc.201000077 Megjegyzés-22172270 DI: 10.1002/cmdc.201000077 Megjegyzés-22183394 DI: 10.1002/cmdc.201000077 Megjegyzés-22189228 DI: 10.1002/cmdc.201000077 Megjegyzés-22194325 DI: 10.1002/cmdc.201000077 Megjegyzés-22209449 DI: 10.1002/cmdc.201000077 Megjegyzés-22209515 DI: 10.1002/cmdc.201000077 Megjegyzés-22217293 DI: 10.1002/cmdc.201000077 Megjegyzés-22225309 DI: 10.1002/cmdc.201000077 Megjegyzés-22226587 DI: 10.1002/cmdc.201000077 Megjegyzés-22226592 DI: 10.1002/cmdc.201000077 Megjegyzés-22558903 DI: 10.1002/cmdc.201000077 Megjegyzés-22559221 DI: 10.1002/cmdc.201000077 Megjegyzés-21161128 M1: Copyright (C) 2011 American Chemical Society (ACS). All Rights Reserved. CAPLUS AN 2010:939085(Journal; General Review) AB - Recent statistics from the World Health Organization indicate that a high percentage of people worldwide suffer from a wide variety of acute or cancer-associated chronic pain. At present, with a few exceptions, the treatment of severe pain relies upon oral administration of the mu-opioid receptor-targeting opiate morphine and its surrogates under strict clinical control. In spite of the powerful in vivo efficacy of these drugs, their long-term use is limited by antinociceptive tolerance, physical dependence, and respiratory depression that evolve. As no analgesics with moderate side effect profiles are currently available for the therapy of different types of pain and stages of cancer, considerable efforts must be made in the search for opiate substitutes. Following the recognition that endogenous peptide ligands of the opioid receptors exert striking effects in various pain models, and with the recent advances in chemical synthesis methods, research interest has steadily moved toward peptide-based compounds as potential opioid analgesics. The endomorphins are an attractive set of endogenous opioid peptides that may meet the requirements of opioid-based pain management. By virtue of their excellent mu-opioid receptor labeling and favorable analgesic properties, these tetrapeptides have gained attention in recent years as potential lead compounds. The ever-increasing number of publications in this field strongly suggests that modified analogues of endomorphins could serve as potent substitutes for opiates, with a lower propensity to induce side effects. This review surveys the main results achieved over the past decade regarding the design, radiolabeling, pharmacological characterization, and structure-activity features of a large body of endomorphin derivatives. LA - English DB - MTMT ER - TY - JOUR AU - Ruiz-Gomez, Gloria AU - Tyndall, Joel D. A. AU - Pfeiffer, Bernhard AU - Abbenante, Giovanni AU - Fairlie, David P. TI - Update 1 of: Over One Hundred Peptide-Activated G Protein-Coupled Receptors Recognize Ligands with Turn Structure JF - CHEMICAL REVIEWS J2 - CHEM REV VL - 110 PY - 2010 IS - 4 SP - PR1 EP - PR41 PG - 41 SN - 0009-2665 DO - 10.1021/cr900344w UR - https://m2.mtmt.hu/api/publication/33643106 ID - 33643106 N1 - Funding Agency and Grant Number: ARC; NHMRC; MEC; FECYT (Spain) Funding text: We thank Tessa Nall for help preparing the original text, and the ARC and NHMRC are gratefully acknowledged for financial support. D.P.F. thanks ARC for a Federation Fellowship, and G.R.-G. thanks the MEC and FECYT (Spain) for postdoctoral fellowship support. 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JF - CHEMICAL REVIEWS J2 - CHEM REV VL - 111 PY - 2010 IS - 2 SP - 657 EP - 687 PG - 31 SN - 0009-2665 DO - 10.1021/cr100100x UR - https://m2.mtmt.hu/api/publication/21162819 ID - 21162819 N1 - ISSN:0009-2665 LA - English DB - MTMT ER - TY - JOUR AU - Bodnar, Richard J TI - Endogenous opiates and behavior: 2008 JF - PEPTIDES J2 - PEPTIDES VL - 30 PY - 2009 IS - 12 SP - 2432 EP - 2479 PG - 48 SN - 0196-9781 DO - 10.1016/j.peptides.2009.09.027 UR - https://m2.mtmt.hu/api/publication/26522143 ID - 26522143 N1 - Cited By :32 Export Date: 6 April 2023 CODEN: PEPTD Correspondence Address: Bodnar, R.J.; Department of Psychology, 65-30 Kissena Blvd, Flushing, NY 11367, United States; email: richard.bodnar@qc.cuny.edu LA - English DB - MTMT ER - TY - JOUR AU - Janecka, A AU - Perlikowska, R AU - Gach, K AU - Fichna, J AU - Mazur, A AU - Kruszynski, R AU - Janecki, T AU - Jankowski, S TI - Structural studies of position 2 modified endomorphin-2 analogs by nmr spectroscopy and molecular modeling JF - POLISH JOURNAL OF CHEMISTRY J2 - POL J CHEM VL - 83 PY - 2009 IS - 7 SP - 1293 EP - 1307 PG - 15 SN - 0137-5083 UR - https://m2.mtmt.hu/api/publication/22217296 ID - 22217296 LA - English DB - MTMT ER - TY - JOUR AU - Perlikowska, R AU - Gach, K AU - Fichna, J AU - Tóth, Géza AU - Walkowiak, B AU - do-Rego, JC AU - Janecka, A TI - Biological activity of endomorphin and [dmt(1)] endomorphin analogs with six-membered proline surrogates in position 2 JF - BIOORGANIC & MEDICINAL CHEMISTRY J2 - BIOORGAN MED CHEM VL - 17 PY - 2009 IS - 11 SP - 3789 EP - 3794 PG - 6 SN - 0968-0896 DO - 10.1016/j.bmc.2009.04.046 UR - https://m2.mtmt.hu/api/publication/1920710 ID - 1920710 N1 - Megjegyzés-22209519 DI: 10.1016/j.bmc.2009.04.046 Megjegyzés-22217299 DI: 10.1016/j.bmc.2009.04.046 LA - English DB - MTMT ER - TY - JOUR AU - Saavedra, C AU - Hernandez, R AU - Boto, A AU - Alvarez, E TI - Catalytic, one-pot synthesis of beta-amino acids from alpha-amino acids. preparation of alpha,beta-peptide derivatives JF - JOURNAL OF ORGANIC CHEMISTRY J2 - J ORG CHEM VL - 74 PY - 2009 IS - 13 SP - 4655 EP - 4665 PG - 11 SN - 0022-3263 DO - 10.1021/jo9004487 UR - https://m2.mtmt.hu/api/publication/20685193 ID - 20685193 N1 - Instituto de Productos Naturales Y Agrobiología del CSIC, Avda. Astrofísico Francisco Sánchez 3, 38206-La Laguna, Tenerife, Spain Instituto de Investigaciones Químicas (CSIC-USe), Isla de la Cartuja, Avda. Américo Vespucio 49, 41092-Sevilla, Spain Cited By :45 Export Date: 5 July 2023 CODEN: JOCEA Correspondence Address: Hernández, R.; Instituto de Productos Naturales Y Agrobiología del CSIC, Avda. Astrofísico Francisco Sánchez 3, 38206-La Laguna, Tenerife, Spain Chemicals/CAS: Oligopeptides LA - English DB - MTMT ER - TY - JOUR AU - Torino, D AU - Mollica, A AU - Pinnen, F AU - Lucente, G AU - Feliciani, F AU - Davis, P AU - Lai, J AU - Ma, SW AU - Porreca, F AU - Hruby, VJ TI - Synthesis and evaluation of new endomorphin analogues modified at the pro(2) residue JF - BIOORGANIC & MEDICINAL CHEMISTRY LETTERS J2 - BIOORG MED CHEM LETT VL - 19 PY - 2009 IS - 15 SP - 4115 EP - 4118 PG - 4 SN - 0960-894X DO - 10.1016/j.bmcl.2009.06.008 UR - https://m2.mtmt.hu/api/publication/22217295 ID - 22217295 N1 - DI: 10.1016/j.bmcl.2009.06.008 Megjegyzés-22194326 DI: 10.1016/j.bmcl.2009.06.008 Megjegyzés-22209450 DI: 10.1016/j.bmcl.2009.06.008 Megjegyzés-22209517 DI: 10.1016/j.bmcl.2009.06.008 LA - English DB - MTMT ER -