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 - Németh, Lukács AU - Hegedüs, Zsófia AU - Martinek, Tamás TI - Predicting Order and Disorder for β-Peptide Foldamers in Water JF - JOURNAL OF CHEMICAL INFORMATION AND MODELING J2 - J CHEM INF MODEL VL - 54 PY - 2014 IS - 10 SP - 2776 EP - 2783 PG - 8 SN - 1549-9596 DO - 10.1021/ci5003476 UR - https://m2.mtmt.hu/api/publication/2764648 ID - 2764648 AB - Following a quantitative validation approach, we tested the AMBER ff03 and GAFF force fields with the TIP3P explicit water model in molecular dynamic simulations of beta-peptide foldamers. The test sequences were selected to represent a wide range of folding behavior in water: compact helix, strand mimetic geometry, and the state of disorder. The combination AMBER ff03-TIP3P successfully predicted the experimentally observed conformational properties and reproduced the NOE distances and backbone (3)J coupling data at a good level. GAFF was unable to produce folded structures correctly due to its biased torsion potentials. We can recommend AMBER ff03-TIP3P for simulations involving beta-peptide sequences in aqueous media including ordered and disordered structures. 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 - Fülöp, Ferenc AU - Martinek, Tamás AU - Tóth, Gábor TI - Application of alicyclic beta-amino acids in peptide chemistry JF - CHEMICAL SOCIETY REVIEWS J2 - CHEM SOC REV VL - 35 PY - 2006 IS - 4 SP - 323 EP - 334 PG - 12 SN - 0306-0012 DO - 10.1039/B501173F UR - https://m2.mtmt.hu/api/publication/1012938 ID - 1012938 N1 - Megjegyzés-21956224 Z9: 133 WC: Chemistry, Multidisciplinary Megjegyzés-21957808 Z9: 133 WC: Chemistry, Multidisciplinary CAplus AN 2006:279672; MEDLINE PMID: 16565749 (Journal; General Review; Article; Research Support, Non-U.S. Gov't; Review); AB - The self-organizing beta-peptides have attracted considerable interest in the fields of foldamer chemistry and biochemistry. These compounds exhibit various stable secondary structure motifs that can be exploited to construct biologically active substances and nanostructured tertiary structures. The secondary structures can be controlled via the beta-amino acid sequence, and cyclic beta-amino acid residues play a crucial role in the design. The most important procedures for the preparation of cyclic beta-amino acid monomers and peptides are discussed in this tutorial review. Besides the secondary structure design principles, the methods of folded structure detection are surveyed. LA - English DB - MTMT ER -