TY - JOUR AU - Olajos, Gábor AU - Hetényi, Anasztázia AU - Wéber, Edit AU - Németh, Lukács AU - Szakonyi, Zsolt AU - Fülöp, Ferenc AU - Martinek, Tamás TI - Induced Folding of Protein-Sized Foldameric β-Sandwich Models with Core β-Amino Acid Residues JF - CHEMISTRY-A EUROPEAN JOURNAL J2 - CHEM-EUR J VL - 21 PY - 2015 IS - 16 SP - 6173 EP - 6180 PG - 8 SN - 0947-6539 DO - 10.1002/chem.201405581 UR - https://m2.mtmt.hu/api/publication/2868602 ID - 2868602 N1 - Funding Agency and Grant Number: Hungarian Academy of Sciences (Lendulet program) [LP-2011-009]; Gedeon Richter Plc. [TP7-017]; Hungarian Research Foundation [OTKA K112442]\n Funding text: This work was supported by the Hungarian Academy of Sciences (Lendulet program LP-2011-009), Gedeon Richter Plc. (TP7-017), and the Hungarian Research Foundation (OTKA K112442). Computations were carried out at the HPC Center of the University of Szeged (TAMOP-4.2.2.C-11/1/KONV-2012-0010).\n Funding Agency and Grant Number: Hungarian Academy of Sciences (Lendulet program) [LP-2011-009]; Gedeon Richter Plc. [TP7-017]; Hungarian Research FoundationOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA K112442] Funding text: This work was supported by the Hungarian Academy of Sciences (Lendulet program LP-2011-009), Gedeon Richter Plc. (TP7-017), and the Hungarian Research Foundation (OTKA K112442). Computations were carried out at the HPC Center of the University of Szeged (TAMOP-4.2.2.C-11/1/KONV-2012-0010). CAplus AN 2015:484036; MEDLINE PMID: 25677195 (Journal; Article; Research Support, Non-U.S. Gov't); AB - The mimicry of protein-sized β-sheet structures with unnatural peptidic sequences (foldamers) is a considerable challenge. In this work, the de novo designed betabellin-14 β-sheet has been used as a template, and α→β residue mutations were carried out in the hydrophobic core (positions 12 and 19). β-Residues with diverse structural properties were utilized: Homologous β3-amino acids, (1R,2S)-2-aminocyclopentanecarboxylic acid (ACPC), (1R,2S)-2-aminocyclohexanecarboxylic acid (ACHC), (1R,2S)-2-aminocyclohex-3-enecarboxylic acid (ACEC), and (1S,2S,3R,5S)-2-amino-6,6-dimethylbicyclo[3.1.1]heptane-3-carboxylic acid (ABHC). Six α/β-peptidic chains were constructed in both monomeric and disulfide-linked dimeric forms. Structural studies based on circular dichroism spectroscopy, the analysis of NMR chemical shifts, and molecular dynamics simulations revealed that dimerization induced β-sheet formation in the 64-residue foldameric systems. Core replacement with (1R,2S)-ACHC was found to be unique among the β-amino acid building blocks studied because it was simultaneously able to maintain the interstrand hydrogen-bonding network and to fit sterically into the hydrophobic interior of the β-sandwich. The novel β-sandwich model containing 25% unnatural building blocks afforded protein-like thermal denaturation behavior. Dissolving sandwiches: A water-soluble β-sandwich has been constructed by using cyclic β-amino acids in the hydrophobic core (see figure). The structural stability is highly dependent on the side-chain, and the destructuring effects of the β-residues could be minimized by using (1R,2S)-2-aminocyclohexanecarboxylic acid. The β-sandwich displays protein-like thermal denaturation behavior. 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 - Katona, Máté AU - Vízvári, Eszter AU - Németh, Lukács AU - Facskó, Andrea AU - Venglovecz, Viktória AU - Rakonczay, Zoltán AU - Hegyi, Péter AU - Tóth-Molnár, Edit TI - Experimental evidence of fluid secretion of rabbit lacrimal gland duct epithelium JF - INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE J2 - INVEST OPHTH VIS SCI VL - 55 PY - 2014 IS - 7 SP - 4360 EP - 4367 PG - 8 SN - 0146-0404 DO - 10.1167/iovs.14-14025 UR - https://m2.mtmt.hu/api/publication/2603674 ID - 2603674 N1 - 1st Department of Internal Medicine, University of Szeged, Szeged, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Department of Ophthalmology, University of Szeged, Szeged, Hungary Department of Medicinal Chemistry, University of Szeged, Szeged, Hungary Cited By :8 Export Date: 26 January 2024 CODEN: IOVSD Correspondence Address: Tóth-Molnár, E.; Department of Ophthalmology, University of Szeged, Korányi fasor 10-11, 6720 Szeged, Hungary; email: tme@tmedit.hu AB - Purpose. To investigate the osmotic water permeability of lacrimal gland (LG) duct epithelium by means of calculation of filtration permeability and to investigate LG ductal fluid secretion. Methods. Experiments were performed on isolated rabbit LG duct segments maintained in short term culture. Osmotically determined fluid movement or fluid secretion into the closed intraluminal space of cultured LG interlobular ducts was analyzed using video microscopic technique. Results. The end of the LG ducts sealed after overnight incubation forming a closed luminal space. For the calculation of osmotic water permeability, ducts were initially perfused with isotonic HEPES-buffered solution, and then with hypotonic HEPES-buffered solution. Filtration permeability was calculated from the initial slope of the relative volume increase. Secretory responses to carbachol or to forskolin stimulation were also investigated. Forskolin stimulation resulted in a rapid and sustained secretory response in both solutions. Forskolin-stimulated fluid secretion was completely inhibited by bumetanide both in HEPES-buffered and in HCO3-/CO2- buffered solutions, suggesting the central role of Na+-K+-2Cl- cotransporter type 1 (NKCC1). Administration of carbachol initiated a rapid but short secretory response in both HEPES buffered and in HCO3-/CO2 buffered solutions. Atropine completely abolished the carbachol-evoked fluid secretion. Conclusions. New method was introduced to investigate LG duct function. Water permeability of rabbit LG duct epithelium was measured by calculating filtration permeability. Fluid secretion of LG duct cells induced by carbachol or forskolin was also demonstrated. These results provide calculated values of lacrimal duct osmotic permeability and direct experimental evidence of LG duct fluid secretion. LA - English DB - MTMT ER - TY - JOUR AU - Hegedüs, Zsófia AU - Wéber, Edit AU - Kriston-Pál, Éva AU - Makra, Ildikó AU - Czibula, Ágnes AU - Monostori, Éva AU - Martinek, Tamás TI - Foldameric α/β-Peptide Analogs of the β-Sheet-Forming Antiangiogenic Anginex: Structure and Bioactivity JF - JOURNAL OF THE AMERICAN CHEMICAL SOCIETY J2 - J AM CHEM SOC VL - 135 PY - 2013 IS - 44 SP - 16578 EP - 16584 PG - 7 SN - 0002-7863 DO - 10.1021/ja408054f UR - https://m2.mtmt.hu/api/publication/2459240 ID - 2459240 AB - The principles of beta-sheet folding and design for alpha-peptidic sequences are well established, while those for sheet mimetics containing homologated amino acid building blocks are still under investigation. To reveal the structure-function relations of beta-amino-acid-containing foldamers, we followed a top-down approach to study a series of alpha/beta-peptidic analogs of anginex, a beta-sheet-forming antiangiogenic peptide. Eight anginex analogs were developed by systematic alpha --> beta(3) substitutions and analyzed by using NMR and CD spectroscopy. The foldamers retained the beta-sheet tendency, though with a decreased folding propensity. beta-Sheet formation could be induced by a micellar environment, similarly to that of the parent peptide. The destructuring effect was higher when the alpha --> beta(3) exchange was located in the beta-sheet core. Analysis of the beta-sheet stability versus substitution pattern and the local conformational bias of the bulky beta(3)V and beta(3)I residues revealed that a mismatch between the H-bonding preferences of the alpha- and beta-residues played a minor role in the structure-breaking effect. Temperature-dependent CD and NMR measurements showed that the hydrophobic stabilization was scaled-down for the alpha/beta-peptides. Analysis of the biological activity of the foldamer peptides showed that four anginex derivatives dose-dependently inhibited the proliferation of a mouse endothelial cell line. The alpha --> beta(3) substitution strategy applied in this work can be a useful approach to the construction of bioactive beta-sheet mimetics with a reduced aggregation tendency and improved pharmacokinetic properties. LA - English DB - MTMT ER - TY - JOUR AU - Szolnoki, Éva Tünde AU - Hetényi, Anasztázia AU - Mándity, István AU - Fülöp, Ferenc AU - Martinek, Tamás TI - Foldameric β-H18/20P mixed helix stabilized by head-to-tail contacts: A way to higher-order structures Foldameric-H18/20P Mixed Helix Stabilized by Head-to-Tail Contacts: A Way to Higher-Order Structures JF - EUROPEAN JOURNAL OF ORGANIC CHEMISTRY J2 - EUR J ORG CHEM VL - 2013 PY - 2013 IS - 17 SP - 3555 EP - 3559 PG - 5 SN - 1434-193X DO - 10.1002/ejoc.201201633 UR - https://m2.mtmt.hu/api/publication/2347492 ID - 2347492 N1 - Funding Agency and Grant Number: European Union (EU) (COST Action) [CM0803]; Hungarian Research Foundation [OTKA PD83600, K83882]; Hungarian Academy of Sciences [LP-2011-009]; Gedeon Richter Centennial Foundation\n Funding text: This work was supported by the European Union (EU) (COST Action CM0803), the Hungarian Research Foundation (OTKA PD83600 and K83882), and the Hungarian Academy of Sciences (Lendulet programme, LP-2011-009). E. S. acknowleges support by the Gedeon Richter Centennial Foundation.\n WoS:hiba:000320036300015 2019-12-11 20:24 cím nem egyezik Funding Agency and Grant Number: European Union (EU) (COST Action)European Union (EU) [CM0803]; Hungarian Research FoundationOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA PD83600, K83882]; Hungarian Academy of SciencesHungarian Academy of Sciences [LP-2011-009]; Gedeon Richter Centennial Foundation Funding text: This work was supported by the European Union (EU) (COST Action CM0803), the Hungarian Research Foundation (OTKA PD83600 and K83882), and the Hungarian Academy of Sciences (Lendulet programme, LP-2011-009). E. S. acknowleges support by the Gedeon Richter Centennial Foundation. AB - Peptidic foldamers are known to exhibit increased diversity in the periodic secondary-structure space in comparison with their natural counterparts, but their higher-order self-organization has been studied less thoroughly. In theory, large-diameter peptide foldamer helices have the capability of self-recognition through axial helix-helix interactions (e.g., head-to-tail), but this phenomenon has previously been observed in only one instance. In this article we report on the discovery of the largest-diameter β-peptidic mixed helix to date, the H18/20P helix. Its formation is solvent-dependent and its folding occurs cooperatively through head-to-tail self-assembly in solution. These findings suggest that axial helix-helix interactions can serve as a new mode for the formation of tertiary/quaternary structures for peptide foldamers, which also show higher-order structural diversity than natural proteins. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. LA - English DB - MTMT ER - TY - JOUR AU - Csillag, Kinga Karola AU - Németh, Lukács AU - Martinek, Tamás AU - Szakonyi, Zsolt AU - Fülöp, Ferenc TI - Stereoselective synthesis of pinane-type tridentate aminodiols and their application in the enantioselective addition of diethylzinc to benzaldehyde JF - TETRAHEDRON-ASYMMETRY J2 - TETRAHEDRON ASYMMETR VL - 23 PY - 2012 IS - 2 SP - 144 EP - 150 PG - 7 SN - 0957-4166 DO - 10.1016/j.tetasy.2012.01.020 UR - https://m2.mtmt.hu/api/publication/1955481 ID - 1955481 N1 - WC: Chemistry, Inorganic & Nuclear; Chemistry, Organic; Chemistry, Physical Funding Agency and Grant Number: Hungarian Research FoundationOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA NK81371, TAMOP-4.2.1/B-09/1/KONV-2010-0005]; Bolyai Janos FellowshipHungarian Academy of Sciences Funding text: We are grateful to the Hungarian Research Foundation (OTKA NK81371) and TAMOP-4.2.1/B-09/1/KONV-2010-0005 for financial support and acknowledge the receipt of a Bolyai Janos Fellowship for Zsolt Szakonyi. Tamas A. Martinek acknowledges HAS Lendulet Foldamer research group. CAplus AN 2012:381772 (Journal); AB - A library of pinane-based aminodiols were prepared from commercially available (1R)-(-)-myrtenol (-)-1. Compound (-)-1 was transformed into ally! trichloroacetamide (+)-2 via the acetimidate, followed by the Overman rearrangement. In order obtain the aminodiol structure, (+)-2 was subjected to stereoselective dihydroxylation with OsO4, resulting in dihydroxy trichloroacetamide (+)-3. The trichloroacetyl group was removed from (+)-3 with aqueous HCl and the (1R,2R,3S,5R)-3-amino-2-hydroxymethyl-6,6-dimethylbicyclo[3.1.1]heptan-2-ol hydrochloride (-)-4 obtained was transformed to primary, secondary and tertiary aminodiols by reductive amination, N-alkylation of aminodiol (+)-9 and debenzylation of N-benzyl aminodiol (+)-10, respectively. In the reactions of (+)-9 and (+)-14 with formaldehyde, highly regioselective ring closure was observed. In contrast with earlier results, the aminodiols gave pinane-fused oxazolidines (+)-11 and (-)-15. The aminodiols and their oxazolidine derivatives 5-15 were applied as chiral catalysts in the enantioselective addition of diethylzinc to benzaldehyde. The best enantioselectivity was observed in the case of the N-benzyl-substituted derivative (+)-9. (C) 2012 Elsevier Ltd. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Berlicki, Ł AU - Pilsl, L AU - Wéber, Edit AU - Mándity, István AU - Cabrele, C AU - Martinek, Tamás AU - Fülöp, Ferenc AU - Reiser, O TI - Unique α,β- and α,α,β,β-peptide foldamers based on cis-β-aminocyclopentanecarboxylic acid JF - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION J2 - ANGEW CHEM INT EDIT VL - 51 PY - 2012 IS - 9 SP - 2208 EP - 2212 PG - 5 SN - 1433-7851 DO - 10.1002/anie.201107702 UR - https://m2.mtmt.hu/api/publication/1926671 ID - 1926671 N1 - Universität Regensburg, Institut für Organische Chemie, Universitätsstrasse 31, 93053 Regensburg, Germany Department of Bioorganic Chemistry, Wrocław University of Technology, 50-370 Wrocław, Poland Institute of Pharmaceutical Chemistry, University of Szeged, 6720 Szeged, Hungary Faculty of Chemistry and Biochemistry, Ruhr University Bochum, 44801 Bochum, Germany Paris Lodron University Salzburg, Department of Molecular Biology, Billrothstrasse 11, 5020 Salzburg, Austria Cited By :69 Export Date: 1 October 2021 CODEN: ACIEF Correspondence Address: Martinek, T.A.; Institute of Pharmaceutical Chemistry, , 6720 Szeged, Hungary; email: martinek@pharm.u-szeged.hu Chemicals/CAS: cycloleucine, 52-52-8; Cycloleucine, 52-52-8; Peptides AB - Waterproof: cis-β-Aminocylopentanecarboxylic acid is a highly suitable building block for the synthesis of α,β- and α,α,β, β-peptides that have unique helical structures with high stability in methanol and aqueous media. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. LA - English DB - MTMT ER - TY - JOUR AU - Martinek, Tamás AU - Fülöp, Ferenc TI - Peptidic foldamers: ramping up diversity JF - CHEMICAL SOCIETY REVIEWS J2 - CHEM SOC REV VL - 41 PY - 2012 IS - 2 SP - 687 EP - 702 PG - 16 SN - 0306-0012 DO - 10.1039/c1cs15097a UR - https://m2.mtmt.hu/api/publication/1842290 ID - 1842290 N1 - Funding Agency and Grant Number: Hungarian Research FoundationOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [NK81371, K83882, TAMOP-4.2.1/B-09/1/KONV-2010-0005]; COSTEuropean Cooperation in Science and Technology (COST) [CM0803]; Janos Bolyai FellowshipHungarian Academy of Sciences; HAS [LP2011-009/2011] Funding text: We thank the Hungarian Research Foundation (NK81371 and K83882), TAMOP-4.2.1/B-09/1/KONV-2010-0005 and COST (CM0803) for financial support. T.A.M. acknowledges the Janos Bolyai Fellowship and the "Lendulet'' programme (LP2011-009/2011) from the HAS. CAplus AN 2012:19612; MEDLINE PMID: 21769415 (Journal; General Review; Article; Research Support, Non-U.S. Gov't; Review); AB - Non-natural folded polymers (foldamers) display considerable versatility, and the design of such molecules is of great current interest. In this respect, peptidic foldamers are perhaps the best-characterized systems, as they populate a number of residue-controlled secondary structures, which have found various biological applications and have also led to the creation of nanostructured materials. This critical review covers recent developments related to diverse building blocks and modern foldamer design principles, such as the stereochemical patterning methods. The recent achievements concerning tertiary/quaternary structures and the self-assembling foldameric nanostructures are also addressed (176 references). LA - English DB - MTMT ER - TY - JOUR AU - Szolnoki, Éva Tünde AU - Hetényi, Anasztázia AU - Martinek, Tamás AU - Szakonyi, Zsolt AU - Fülöp, Ferenc TI - Self-association-driven transition of the β-peptidic H12 helix to the H18 helix JF - ORGANIC & BIOMOLECULAR CHEMISTRY J2 - ORG BIOMOL CHEM VL - 10 PY - 2012 IS - 2 SP - 255 EP - 259 PG - 5 SN - 1477-0520 DO - 10.1039/c1ob06627g UR - https://m2.mtmt.hu/api/publication/1842289 ID - 1842289 AB - Various patterns of foldameric oligomers formed by trans-ABHC ((1S,2S,3S, 5S)-2-amino-6,6-dimethylbicyclo-[3.3.1]heptane-3-carboxylic acid) and beta(3)-hSer residues were studied. NMR, ECD and molecular modelling demonstrated that octameric and nonameric sequences with multiple i-i+3 ABHC pair repulsions attain the beta-H18 helix in CD3OH. As a close relative of the alpha-helix, this helix type is stabilized by i-i+4 backbone H-bond interactions. The formation of the beta-H18 helix was found to be solvent-and concentration-dependent. Upon dilution, the beta-H18 -> beta-H12 helix transition was revealed by concentration-dependent ECD, DOSY-NMR and TEM measurements. LA - English DB - MTMT ER -