TY - JOUR AU - Nagy, Adrienn AU - Csordás, Barbara AU - Zsoldos-Mády, Virág AU - Pintér, István AU - Farkas, Viktor AU - Perczel, András TI - C-3 epimers of sugar amino acids as foldameric building blocks: improved synthesis, useful derivatives, coupling strategies JF - AMINO ACIDS J2 - AMINO ACIDS VL - 49 PY - 2017 IS - 2 SP - 223 EP - 240 PG - 18 SN - 0939-4451 DO - 10.1007/s00726-016-2346-5 UR - https://m2.mtmt.hu/api/publication/3134571 ID - 3134571 N1 - Megjegyzés-26507583 N1 Funding details: NK101072, OTKA, Országos Tudományos Kutatási Alapprogramok Funding Agency and Grant Number: Hungarian Scientific Research FundOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA NK101072] Funding text: The authors gratefully acknowledge Szebasztian Szaniszlo for his contribution to the preparative work and Prof. Imre G Csizmadia for helpful discussion. The authors wish to thank Laszlo Kocsis and Gabor Szirbik from ThalesNano Inc. (Budapest, Hungary) for their help and advice in hydrogenation reaction and for their support with the equipment, and Anita Kapros for her help in MS measurements. This work was supported by Grants from the Hungarian Scientific Research Fund (OTKA NK101072). AB - To obtain key sugar derivatives for making homooligomeric foldamers or α/β-chimera peptides, economic and multigram scale synthetic methods were to be developed. Though described in the literature, the cost-effective making of both 3-amino-3-deoxy-ribofuranuronic acid (H–t X–OH) and its C-3 epimeric stereoisomer, the 3-amino-3-deoxy-xylofuranuronic acid (H–c X–OH) from d-glucose is described here. The present synthetic route elaborated is (1) appropriate for large-scale synthesis; (2) reagent costs reduced (e.g. by a factor of 400); (3) yields optimized are ~80% or higher for all six consecutive steps concluding –t X– or –c X– and (4) reaction times shortened. Thus, a new synthetic route step-by-step optimized for yield, cost, time and purification is given both for d-xylo and d-ribo-amino-furanuronic acids using sustainable chemistry (e.g. less chromatography with organic solvents; using continuous-flow reactor). Our study encompasses necessary building blocks (e.g. –X–OMe, –X–OiPr, –X–NHMe, Fmoc–X–OH) and key coupling reactions making –Aaa–t X–Aaa– or –Aaa–t X–t X–Aaa– type “inserts”. Completed for both stereoisomers of X, including the newly synthesized Fmoc–c X–OH, producing longer oligomers for drug design and discovery is more of a reality than a wish. LA - English DB - MTMT ER - TY - JOUR AU - Csordás, Barbara AU - Nagy, Adrienn AU - Harmat, Veronika AU - Zsoldos-Mády, Virág AU - Leveles, Ibolya AU - Pintér, István AU - Farkas, Viktor AU - Perczel, András TI - Origin of problems related to Staudinger reduction in carbopeptoid syntheses JF - AMINO ACIDS J2 - AMINO ACIDS VL - 48 PY - 2016 IS - 11 SP - 2619 EP - 2633 PG - 15 SN - 0939-4451 DO - 10.1007/s00726-016-2289-x UR - https://m2.mtmt.hu/api/publication/3098290 ID - 3098290 N1 - Megjegyzés-26182763 10.1007/s00726-016-2289-x AB - We report the solid phase synthesis of –GG-X-GG– type α/β-carbopeptoids incorporating RibAFU(ip) (1a, tX) or XylAFU(ip) (2a, cX) sugar amino acids. Though coupling efficacy is moderate, both the lengthier synthetic route using Fmoc derivative (e.g., Fmoc-RibAFU(ip)-OH) and the azido derivative (e.g., N3-RibAFU(ip)-OH) via Staudinger reaction with nBu3P can be successfully applied. Both X-ray diffraction, 1H- and 31P-NMR, and theoretical (QM) data support and explain why the application of Ph3P as Staudinger reagent is “ineffective” in the case of a cis stereoisomer, if cX is attached to the preceding residue with a peptide (–CONH–) bond. The failure of the polypeptide chain elongation with N3-cX originates from the “coincidence” of a steric crowdedness and an electronic effect disabling the mandatory nucleophilic attack during the hydrolysis of a quasi penta-coordinated triphenylphosphinimine. Nevertheless, the synthesis of the above α/β-chimera peptides as completed now by a new pathway via 1,2-O-isopropylidene-3-azido-3-deoxy-ribo- and -xylo-furanuronic acid (H-RibAFU(ip)-OH 1a and H-XylAFU(ip)-OH 2a) coupled with N-protected α-amino acids on solid phase could serve as useful examples and starting points of further synthetic efforts. © 2016 Springer-Verlag Wien LA - English DB - MTMT ER - 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 - 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 - Beke-Somfai, Tamás AU - Somlai, Csaba AU - Perczel, András TI - Toward a rational design of beta-peptide structures JF - JOURNAL OF COMPUTATIONAL CHEMISTRY J2 - J COMPUT CHEM VL - 27 PY - 2006 IS - 1 SP - 20 EP - 38 PG - 19 SN - 0192-8651 DO - 10.1002/jcc.20299 UR - https://m2.mtmt.hu/api/publication/1056989 ID - 1056989 N1 - Megjegyzés-21956216 Z9: 17 WC: Chemistry, Multidisciplinary AB - Intrinsic: conformational characteristics of beta-peptides built up from simple achiral and chiral P-amino acid residues (i.e., HCO-beta-Ala-NH2, HCO-beta-Abu-NH2) were studied using quantum chemical calculations and H-1-NMR spectroscopy. A conformer-based systematic and uniform nomenclature was introduced to differentiate conformers. Geometry optimizations were performed on all homoconformers of both HCO-(beta-Ala)k-NH2 and HCO-(beta-AbU)(k)-NH2 (1 <= k <= 6) model systems at the RHF/3-21G and RHF/6-311+ +G(d, p) levels of theory. To test for accuracy and precision, additional. computations were carried out at several levels of theory [e.g., RHF/6-31G(d), and B3LYP/6-311+ +G(d, p)]. To display the folding preference, the relative stability of selected conformers as function of the length of the polypeptide chain was determined. Ab initio population distribution of hexapeptides and the conformational ensemble of synthetic models composed of beta-Ala and beta-Abu studied using H-1-NMR in different solvents were compared at a range of temperatures. Helical preference induced by various steric effects of nonpolar side chains was tested using higher level ab initio methods for well-known model systems such as: HCO-(beta-HVal-beta-HAla-beta-HLeu)(2)-NH2, HCO-(ACHC)(6)-NH2, HCO-(trans-ACPC)(6)-NH2, and HCO-(cis-ACPC)(6)-NH2. The relative stabilities determined by theoretical methods agreed well with most experimental data, supporting the theory that the local conformational preference influenced by steric effects is a key determining factor of the global fold both in solution and in the gas phase. 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 - TY - JOUR AU - Martinek, Tamás AU - Mándity, István AU - Fülöp, Lívia AU - Tóth, Gábor AU - Vass, Elemér AU - Hollósi, Miklós AU - Forró, Enikő AU - Fülöp, Ferenc TI - Effects of the alternating backbone configuration on the secondary structure and self-assembly of beta-peptides JF - JOURNAL OF THE AMERICAN CHEMICAL SOCIETY J2 - J AM CHEM SOC VL - 128 PY - 2006 IS - 41 SP - 13539 EP - 13544 PG - 6 SN - 0002-7863 DO - 10.1021/ja063890c UR - https://m2.mtmt.hu/api/publication/1078988 ID - 1078988 AB - Heterochiral homo-oligomers with alternating backbone configurations were constructed by using the different enantiomers of the cis- and trans-2-aminocyclopentanecarboxylic acid (ACPC) monomers. Molecular modeling and the spectroscopic techniques (NMR, ECD, and VCD) unequivocally proved that the alternating heterochiral cis-ACPC sequences form an H10/12 helix, where extra stabilization can be achieved via the cyclic side chains. The ECD and TEM measurements, together with molecular modeling, revealed that the alternating heterochiral trans-ACPC oligomers tend to attain a polar-strand secondary structure in solution, which can self-assemble into nanostructured fibrils. The observations indicate that coverage of all the possible secondary structures (various helix types and strand-mimicking conformations) can be attained with the help of cyclic beta-amino acid diastereomers. A relationship has been established between the backbone chirality pattern and the prevailing secondary structure, which underlines the role of stereochemical control in the beta-peptide secondary structure design and may contribute to future biological applications. LA - English DB - MTMT ER - TY - JOUR AU - Martinek, Tamás AU - Tóth, Gábor AU - Vass, Elemér AU - Hollósi, Miklós AU - Fülöp, Ferenc TI - cis-2-aminocyclopentanecarboxylic acid oligomers adopt a sheetlike structure: Switch from helix to nonpolar strand JF - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION J2 - ANGEW CHEM INT EDIT VL - 41 PY - 2002 IS - 10 SP - 1718 EP - 1721 PG - 4 SN - 1433-7851 DO - 10.1002/1521-3773(20020517)41:10<1718::AID-ANIE1718>3.0.CO;2-2 UR - https://m2.mtmt.hu/api/publication/1013825 ID - 1013825 LA - English DB - MTMT ER - TY - JOUR AU - Perczel, András AU - Ángyán, János AU - Kajtar, M AU - Viviani, W AU - Rivail, JL AU - Marcoccia, JF AU - Csizmadia, Imre Gyula TI - PEPTIDE MODELS .1. TOPOLOGY OF SELECTED PEPTIDE CONFORMATIONAL POTENTIAL-ENERGY SURFACES (GLYCINE AND ALANINE DERIVATIVES) JF - JOURNAL OF THE AMERICAN CHEMICAL SOCIETY J2 - J AM CHEM SOC VL - 113 PY - 1991 SP - 6256 EP - 6265 PG - 10 SN - 0002-7863 DO - 10.1021/ja00016a049 UR - https://m2.mtmt.hu/api/publication/2758 ID - 2758 AB - N-Formylglycinamide (For-Gly-NH2), N-formyl-L-alaninamide (For-L-Ala-NH2), and N-formyl-D-alaninamide (For-D-Ala-NH2) were subjected to conformational studies by molecular mechanics (MM) and ab initio SCF methods. Both methods predicted the corresponding-gamma (usually labeled as C-7eq) conformations to be the global minimum on the Ramachandran map, E(phi,psi). The number of minima and their approximate location obtained by MM corresponded to those that one might have expected on the basis of multidimensional conformation analysis. However, only the ab initio SCF study was capable of properly describing the effects associated with excessive repulsive or attractive interactions that lead to the annihilation and creation of certain critical points. Consequently, the topology of the MM and SCF conformational potential energy surfaces, E(phi,psi), were found to be remarkably different for the three diamide systems investigated in this work. LA - English DB - MTMT ER -