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 - Leitgeb, Balázs TI - Conformational Similarities and Dissimilarities Between the Stereoisomeric Forms of Endomorphin-2 JF - CHEMICAL BIOLOGY & DRUG DESIGN J2 - CHEM BIOL DRUG DES VL - 79 PY - 2012 IS - 3 SP - 313 EP - 325 PG - 13 SN - 1747-0277 DO - 10.1111/j.1747-0285.2011.01275.x UR - https://m2.mtmt.hu/api/publication/2015332 ID - 2015332 N1 - WoS:hiba:000299253200009 2019-03-03 19:37 első szerző nem egyezik AB - In this study, taking into account both the ld and cistrans isomerisms, a comprehensive structural characterization and a comparative conformational analysis were performed on the 32 stereoisomeric forms of opioid tetrapeptide, endomorphin-2. For all stereoisomers, the F-? and ? conformational spaces were explored, in the course of which the conformational distributions, as well as the rotamer states of aromatic side chains were characterized in detail. Furthermore, the typical beta- and ?-turn structures, as well as the characteristic intramolecular interactions (i.e., H-bonds, aromaticaromatic and prolinearomatic interplays) were determined. The afore-mentioned structural and conformational features identified for each stereoisomeric form were compared with one another, considering all 32 stereoisomers. The results obtained from this comparative study indicated that both similarities and dissimilarities could be observed between the stereoisomeric forms, with regard to their structural and conformational properties. This theoretical work supplied several valuable observations concerning the effects of both ld and cistrans isomerisms on the three-dimensional structure of parent peptide and its stereoisomers. Nevertheless, in the course of this structural investigation, it was clarified how the structural and conformational features of stereoisomeric forms differed from one another. LA - English DB - MTMT ER - TY - JOUR AU - Leitgeb, Balázs TI - Spatial relationships between the pharmacophores of endomorphin-2: a comparative study of stereoisomers JF - CENTRAL EUROPEAN JOURNAL OF CHEMISTRY J2 - CENT EUR J CHEM VL - 10 PY - 2012 IS - 6 SP - 1791 EP - 1798 PG - 8 SN - 1895-1066 DO - 10.2478/s11532-012-0105-3 UR - https://m2.mtmt.hu/api/publication/2102717 ID - 2102717 AB - The spatial relationships between the pharmacophore elements were investigated in the case of four different stereoisomeric forms of opioid tetrapeptide, endomorphin-2, taking into account the L-D and cis-trans isomerisms. On the basis of distances and angles measured between the pharmacophoric points, a comparative analysis of conformational distributions was performed, applying a variety of distance-angle maps. The results obtained by this theoretical study indicated that the stereoisomers of endomorphin-2 could be distinguished from one another, based on the comparative analysis of distance-angle maps. Nevertheless, it could be concluded that this method proved to be suitable to examine the effects of L-D and cis-trans isomerisms on the spatial relationships of the pharmacophores of tetrapeptide. LA - English DB - MTMT ER - TY - JOUR AU - Wu, YC AU - Jaglinski, T AU - Hsieh, JY AU - Chiu, JJ AU - Chiang, TY AU - Hwang, CC TI - Four-component pharmacophore model for endomorphins toward mu opioid receptor subtypes JF - JOURNAL OF MOLECULAR MODELING J2 - J MOL MODEL VL - 18 PY - 2012 IS - 2 SP - 825 EP - 834 PG - 10 SN - 1610-2940 DO - 10.1007/s00894-011-1108-2 UR - https://m2.mtmt.hu/api/publication/22834464 ID - 22834464 N1 - Biomedical Engineering Program, Department of Engineering Science, National Cheng Kung University, Tainan 70101, Taiwan Computer Science Program, Department of Mechanical Engineering, Ming Hsin University of Science and Technology, Hsinchu 30401, Taiwan Biomolecular Network Program, Department of Electrical Engineering, National Cheng Kung University, Tainan 70101, Taiwan Neuroscience Program, Department of Life Science, National Cheng Kung University, Tainan 70101, Taiwan Cited By :3 Export Date: 2 May 2023 CODEN: JMMOF Correspondence Address: Hwang, C.-C.; Biomedical Engineering Program, , Tainan 70101, Taiwan; email: chchwang@mail.ncku.edu.tw LA - English DB - MTMT ER - TY - JOUR AU - Whitby, LR AU - Ando, Y AU - Setola, V AU - Vogt, PK AU - Roth, BL AU - Boger, DL TI - Design, Synthesis, and Validation of a beta-Turn Mimetic Library Targeting Protein-Protein and Peptide-Receptor Interactions JF - JOURNAL OF THE AMERICAN CHEMICAL SOCIETY J2 - J AM CHEM SOC VL - 133 PY - 2011 IS - 26 SP - 10184 EP - 10194 PG - 11 SN - 0002-7863 DO - 10.1021/ja201878v UR - https://m2.mtmt.hu/api/publication/23598356 ID - 23598356 N1 - Megjegyzés-22183393 DI: 10.1021/ja201878v Megjegyzés-22194323 DI: 10.1021/ja201878v Megjegyzés-22227656 DI: 10.1021/ja201878v Megjegyzés-22559219 DI: 10.1021/ja201878v 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 - Rincon, DA AU - Cordeiro, MNDS AU - Mosquera, RA TI - Theoretical Study of Morphine and Heroin: Conformational Study in Gas Phase and Aqueous Solution and Electron Distribution Analysis JF - INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY J2 - INT J QUANTUM CHEM VL - 110 PY - 2010 IS - 13 SP - 2472 EP - 2482 PG - 11 SN - 0020-7608 DO - 10.1002/qua.22851 UR - https://m2.mtmt.hu/api/publication/22559220 ID - 22559220 N1 - DI: 10.1002/qua.22851 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, Renata AU - Fichna, Jakub AU - Janecka, Anna TI - Endomorfiny− endogenne ligandy receptora opioidowego μ JF - POSTEPY BIOCHEMII J2 - POSTEPY BIOCHEM VL - 55 PY - 2009 IS - 4 SP - 388 EP - 394 PG - 7 SN - 0032-5422 UR - https://m2.mtmt.hu/api/publication/27132316 ID - 27132316 LA - Polish DB - MTMT ER - TY - JOUR AU - Rincon, DA AU - Cordeiro, MNDS AU - Mosquera, RA TI - On the electronic structure of cocaine and its metabolites JF - JOURNAL OF PHYSICAL CHEMISTRY A J2 - J PHYS CHEM A VL - 113 PY - 2009 IS - 50 SP - 13937 EP - 13942 PG - 6 SN - 1089-5639 DO - 10.1021/jp9056048 UR - https://m2.mtmt.hu/api/publication/22559223 ID - 22559223 N1 - DI: 10.1021/jp9056048 LA - English DB - MTMT ER - TY - JOUR AU - Gentilucci, L AU - Squassabia, F AU - Demarco, R AU - Artali, R AU - Cardillo, G AU - Tolomelli, A AU - Spampinato, S AU - Bedini, A TI - Investigation of the interaction between the atypical agonist c[YpwFG] and MOR JF - FEBS JOURNAL J2 - FEBS J VL - 275 PY - 2008 IS - 9 SP - 2315 EP - 2337 PG - 23 SN - 1742-464X DO - 10.1111/j.1742-4658.2008.06386.x UR - https://m2.mtmt.hu/api/publication/22559225 ID - 22559225 N1 - DI: 10.1111/j.1742-4658.2008.06386.x LA - English DB - MTMT ER - TY - JOUR AU - Wang, YC AU - Wu, YC AU - Chen, JW AU - Huang, LSF AU - Tsai, FR AU - Hwang, CC TI - Structure-activity relationships of modified C-terminal endomorphin-2 analogues by molecular dynamics simulations JF - JOURNAL OF MOLECULAR GRAPHICS AND MODELLING J2 - J MOL GRAPH MODEL VL - 27 PY - 2008 IS - 4 SP - 489 EP - 496 PG - 8 SN - 1093-3263 DO - 10.1016/j.jmgm.2008.08.007 UR - https://m2.mtmt.hu/api/publication/22209521 ID - 22209521 N1 - DI: 10.1016/j.jmgm.2008.08.007 Megjegyzés-22183396 DI: 10.1016/j.jmgm.2008.08.007 Megjegyzés-22194330 DI: 10.1016/j.jmgm.2008.08.007 Megjegyzés-22559224 DI: 10.1016/j.jmgm.2008.08.007 LA - English DB - MTMT ER - TY - JOUR AU - Gao, YF AU - Zhai, MX TI - Studies on structure-activity relationship of endomorphins VL - 2 PY - 2007 IS - 5 SP - 387 EP - 390 PG - 4 UR - https://m2.mtmt.hu/api/publication/22845563 ID - 22845563 LA - Chinese DB - MTMT ER - TY - JOUR AU - Gentilucci, L AU - Squassabia, F AU - Artali, R TI - Re-discussion of the importance of ionic interactions in stabilizing ligand-opioid receptor complex and in activating signal transduction JF - CURRENT DRUG TARGETS J2 - CURR DRUG TARGETS VL - 8 PY - 2007 IS - 1 SP - 185 EP - 196 PG - 12 SN - 1389-4501 DO - 10.2174/138945007779315704 UR - https://m2.mtmt.hu/api/publication/22186309 ID - 22186309 LA - English DB - MTMT ER - TY - JOUR AU - Leitgeb, Balázs TI - Structural investigation of endomorphins by experimental and theoretical methods: Hunting for the bioactive conformation JF - CHEMISTRY & BIODIVERSITY J2 - CHEM BIODIVERS VL - 4 PY - 2007 IS - 12 SP - 2703 EP - 2724 PG - 22 SN - 1612-1872 DO - 10.1002/cbdv.200790221 UR - https://m2.mtmt.hu/api/publication/1915407 ID - 1915407 LA - English DB - MTMT ER - TY - JOUR AU - Li, T AU - Shiotani, K AU - Miyazaki, A AU - Tsuda, Y AU - Ambo, A AU - Sasaki, Y AU - Jinsmaa, Y AU - Marczak, E AU - Bryan, SD AU - Lazarus, LH AU - Okada, Y TI - Bifunctional [2 ',6 '-dimethyl-l-tyrosine(1)]endomorphin-2 Analogues Substituted at Position 3 With Alkylated Phenylalanine Derivatives Yield Potent Mixed Mu-agonist/delta-antagonist And Dual Mu-agonist/delta-agonist Opioid Ligands JF - JOURNAL OF MEDICINAL CHEMISTRY J2 - J MED CHEM VL - 50 PY - 2007 SP - 2753 EP - 2766 PG - 14 SN - 0022-2623 DO - 10.1021/jm061238m UR - https://m2.mtmt.hu/api/publication/22202629 ID - 22202629 LA - English DB - MTMT ER - TY - JOUR AU - Shao, X AU - Gao, YF AU - Zhu, CJ AU - Liu, XH AU - Yao, JL AU - Cui, YX AU - Wang, R TI - Conformational Analysis of Endomorphin-2 Analogs With Phenylalanine Mimics by Nmr And Molecular Modeling JF - BIOORGANIC & MEDICINAL CHEMISTRY J2 - BIOORGAN MED CHEM VL - 15 PY - 2007 IS - 10 SP - 3539 EP - 3547 PG - 9 SN - 0968-0896 DO - 10.1016/j.bmc.2007.02.050 UR - https://m2.mtmt.hu/api/publication/22194337 ID - 22194337 LA - English DB - MTMT ER - TY - JOUR AU - Cardillo, G AU - Gentilucci, L AU - Tolomelli, A TI - Unusual amino acids: Synthesis and introduction into naturally occurring peptides and biologically active analogues JF - MINI-REVIEWS IN MEDICINAL CHEMISTRY J2 - MINI REV MED CHEM VL - 6 PY - 2006 SP - 293 EP - 304 PG - 12 SN - 1389-5575 DO - 10.2174/138955706776073394 UR - https://m2.mtmt.hu/api/publication/22172281 ID - 22172281 LA - English DB - MTMT ER - TY - JOUR AU - Leitgeb, Balázs AU - Tóth, Géza TI - Aromatic-aromatic and proline-aromatic interactions in endomorphin-1 and endomorphin-2 JF - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY J2 - EUR J MED CHEM VL - 40 PY - 2005 SP - 674 EP - 686 PG - 13 SN - 0223-5234 DO - 10.1016/j.ejmech.2004.10.015 UR - https://m2.mtmt.hu/api/publication/1913931 ID - 1913931 LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Géza AU - Keresztes, Attila AU - Tömböly, Csaba AU - Péter, Antal AU - Fülöp, Ferenc AU - Tourwe, D AU - Navratilova, E AU - Varga, Éva AU - Roeske, W R AU - Yamamura, H I AU - Szűcs, Mária AU - Borsodi, Anna TI - New endomorphin analogs with mu-agonist and delta-antagonist properties JF - PURE AND APPLIED CHEMISTRY J2 - PURE APPL CHEM VL - 76 PY - 2004 IS - 5 SP - 951 EP - 957 PG - 7 SN - 0033-4545 DO - 10.1351/pac200476050951 UR - https://m2.mtmt.hu/api/publication/1013246 ID - 1013246 AB - Endomorphins (endomorphin-1, H-Tyr-Pro-Trp-Phe-NH2, endomorphin-2, Tyr-Pro-Phe-Phe-NH2) are potent and selective mu-opioid receptor agonists. In order to improve the affinity and chemical stability of endomorphins, we have designed, synthesized, and characterized novel analogs with unnatural (2', 6'-dimethyltyrosine, Dmt) and/or beta-alicyclic amino acids (ACPC and ACHC). Radioligand binding assay indicated that several of the novel analogs exhibit high affinity for both mu- and delta-opioid receptors in rat- or mouse-brain membrane preparations. The most promising derivatives-such as Dmt-Pro-Trp/Phe-Phe-NH2. Dmt-(1S,2R)-ACPC-Phe-Phe-NH2, and Dmt-(1S,2R)-ACHC-Phe-Phe-NH2)-were characterized in recombinant cell lines expressing human mu- or delta-opioid receptors. Interestingly, while these novel peptides were potent opioid agonists in the functional [S-35]GTPgammaS binding assays in Chinese hamster ovary cells expressing the mu-opioid receptors, some behaved as antagonist or inverse agonist in the human delta-opioid receptor-expressing CHO cells. Since it has previously been demonstrated that the coadministration of delta-antagonists with mu-analgesics attenuates the development of analgesic tolerance, introduction of high-affinity delta-antagonist properties into the mu-agonist endomorphins is expected to lead to potent analgesics that produce limited tolerance. LA - English DB - MTMT ER - TY - JOUR AU - Leitgeb, Balázs AU - Szekeres, András TI - Exploring the conformational space of the μ-opioid agonists endomorphin-1 and endomorphin-2 JF - JOURNAL OF MOLECULAR STRUCTURE: THEOCHEM J2 - J MOL STRUC-THEOCHEM VL - 666-667 PY - 2003 SP - 337 EP - 344 PG - 8 SN - 0166-1280 DO - 10.1016/j.theochem.2003.08.043 UR - https://m2.mtmt.hu/api/publication/1117748 ID - 1117748 LA - English DB - MTMT ER -