TY - THES AU - Nagy, Adrienn TI - C-3 epimer cukoraminosavak és új típusú foldamereik szintézise, szerkezetvizsgálata PB - Eötvös Loránd Tudományegyetem (ELTE) PY - 2020 SP - 163 DO - 10.15476/ELTE.2019.231 UR - https://m2.mtmt.hu/api/publication/31598345 ID - 31598345 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Farkas, Viktor AU - Nagy, Adrienn AU - Karancsiné Menyhárd, Dóra AU - Perczel, András TI - Assignment of Vibrational Circular Dichroism Cross-Referenced Electronic Circular Dichroism Spectra of Flexible Foldamer Building Blocks: Towards Assigning Pure Chiroptical Properties of Foldamers JF - CHEMISTRY-A EUROPEAN JOURNAL J2 - CHEM-EUR J VL - 25 PY - 2019 IS - 65 SP - 14890 EP - 14900 PG - 11 SN - 0947-6539 DO - 10.1002/chem.201903023 UR - https://m2.mtmt.hu/api/publication/30937506 ID - 30937506 N1 - MTA-ELTE Protein Modelling Research Group, Institute of Chemistry, Eötvös Loránd University, Pázmány P. stny. 1/A, Budapest, 1117, Hungary Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány P. stny. 1/A, Budapest, 1117, Hungary Export Date: 5 April 2024 CODEN: CEUJE Correspondence Address: Farkas, V.; MTA-ELTE Protein Modelling Research Group, Pázmány P. stny. 1/A, Hungary; email: farkasv@caesar.elte.hu LA - English DB - MTMT ER - TY - JOUR AU - Goldschmidt Gőz, Viktória AU - Nagy, Adrienn AU - Farkas, Viktor AU - Keszei, Ernő AU - Perczel, András TI - Unwanted hydrolysis or alpha/beta-peptide bond formation: how long should the rate-limiting coupling step take? JF - RSC ADVANCES J2 - RSC ADV VL - 9 PY - 2019 IS - 53 SP - 30720 EP - 30728 PG - 9 SN - 2046-2069 DO - 10.1039/c9ra06124j UR - https://m2.mtmt.hu/api/publication/30859729 ID - 30859729 N1 - Funding Agency and Grant Number: European UnionEuropean Union (EU); State of Hungary; European Regional Development FundEuropean Union (EU) [VEKOP-2.3.2-16-2017-00014]; Janos Bolyai Research Scholarship of the Hungarian Academy of SciencesHungarian Academy of Sciences; Hungarian Academy of SciencesHungarian Academy of Sciences Funding text: The authors wish to thank Daniel Horvath for helping 700 MHz NMR measurements and Tamas Martinek for Fmoc-ACPC-OH, Fmoc-ACHC-OH and linear beta-amino acids. These research projects were supported by the European Union and the State of Hungary and co-financed by the European Regional Development Fund (VEKOP-2.3.2-16-2017-00014). This paper was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (V. Farkas) and MedInProt Grant Facilitating Access to Instruments from the Hungarian Academy of Sciences. Funding Agency and Grant Number: European UnionEuropean Commission; State of Hungary; European Regional Development FundEuropean Commission [VEKOP-2.3.2-16-2017-00014]; Janos Bolyai Research Scholarship of the Hungarian Academy of SciencesHungarian Academy of Sciences; Hungarian Academy of SciencesHungarian Academy of Sciences Funding text: The authors wish to thank Daniel Horvath for helping 700 MHz NMR measurements and Tamas Martinek for Fmoc-ACPC-OH, Fmoc-ACHC-OH and linear beta-amino acids. These research projects were supported by the European Union and the State of Hungary and co-financed by the European Regional Development Fund (VEKOP-2.3.2-16-2017-00014). This paper was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (V. Farkas) and MedInProt Grant Facilitating Access to Instruments from the Hungarian Academy of Sciences. AB - Nowadays, in Solid Phase Peptide Synthesis (SPPS), being either manual, automated, continuous flow or microwave-assisted, the reaction with various coupling reagents takes place via in situ active ester formation. In this study, the formation and stability of these key active esters were investigated with time-resolved H-1 NMR by using the common PyBOP/DIEA and HOBt/DIC coupling reagents for both alpha- and beta-amino acids. Parallel to the amide bond formation, the hydrolysis of the alpha/beta-active esters, a side reaction that is a considerable efficacy limiting factor, was studied. Based on the chemical nature/constitution of the active esters, three amino acid categories were determined: (i) the rapidly hydrolyzing ones (t < 6 h) with smaller (Ala) or even longer side chains (Arg) holding a large protecting group; (ii) branched amino acids (Ile, Thr) with slowly hydrolyzing (6 < t < 24 h) propensities, and (iii) non-hydrolyzing ones, such as the hard-to-couple beta-amino acids or beta-sugar amino acid derivatives, stable for longer times (t > 24 h) in solution. The current insight into the kinetics of this key hydrolysis side reaction serves as a guide to optimize the coupling conditions of alpha- and beta-amino acids, thereby saving time and minimizing the amounts of reagents and amino acids to be used - all key factors of more environmentally friendly chemistry. LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Adrienn AU - Goldschmidt Gőz, Viktória AU - Pintér, István AU - Farkas, Viktor AU - Perczel, András TI - α/β-Chimera peptide synthesis with cyclic β-sugar amino acids: the efficient coupling protocol JF - AMINO ACIDS J2 - AMINO ACIDS VL - 51 PY - 2019 IS - 4 SP - 669 EP - 678 PG - 10 SN - 0939-4451 DO - 10.1007/s00726-019-02702-9 UR - https://m2.mtmt.hu/api/publication/30435771 ID - 30435771 N1 - Funding Agency and Grant Number: Eotvos Lorand University (ELTE); European Union; State of Hungary; European Regional Development Fund [VEKOP-2.3.2-16-2017-00014]; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences; MedInProt Grant Facilitating Access to Instruments from the Hungarian Academy of Sciences Funding text: Open access funding provided by Eotvos Lorand University (ELTE). The authors wish to thank Dora K. Menyhard and Erno Keszei for consulting, Anita Kapros for the MS measurements, and Andras Lang and Daniel Horvath for helping 700 MHz NMR measurements. These research projects were supported by the European Union and the State of Hungary and co-financed by the European Regional Development Fund (VEKOP-2.3.2-16-2017-00014). This paper was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (V. Farkas) and MedInProt Grant Facilitating Access to Instruments from the Hungarian Academy of Sciences. WoS:hiba:000463590400010 2019-04-21 12:29 cím nem egyezik Funding Agency and Grant Number: Eotvos Lorand University (ELTE); European UnionEuropean Commission; State of Hungary; European Regional Development FundEuropean Commission [VEKOP-2.3.2-16-2017-00014]; Janos Bolyai Research Scholarship of the Hungarian Academy of SciencesHungarian Academy of Sciences; MedInProt Grant Facilitating Access to Instruments from the Hungarian Academy of Sciences Funding text: Open access funding provided by Eotvos Lorand University (ELTE). The authors wish to thank Dora K. Menyhard and Erno Keszei for consulting, Anita Kapros for the MS measurements, and Andras Lang and Daniel Horvath for helping 700 MHz NMR measurements. These research projects were supported by the European Union and the State of Hungary and co-financed by the European Regional Development Fund (VEKOP-2.3.2-16-2017-00014). This paper was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (V. Farkas) and MedInProt Grant Facilitating Access to Instruments from the Hungarian Academy of Sciences. AB - The synthesis of α/β-chimeras comprises peptide bond formation from α- to β-, from β- to β-, and from β- to α-amino acid residues. The fine-tuned solid phase synthesis of –GXXG– chimera peptides containing the simplest achiral α-amino acid glycine and two cyclic SAAs of different ring size [X denoting cyclic β-Sugar Amino Acids (β-SAA)] is reported, variants containing Fmoc–RibAFU(ip)–OH a furanoid-, and Fmoc–GlcAPU(Me)–OH a pyranoid-type structural “Lego-element”. Systematic search for the best coupling strategy with both H–β-SAA–OHs is described, including the comparison of the different coupling reagents and conditions. Selecting the optimal reagent (from commonly used PyBOP, HATU and HOBt) was assisted by time-resolved 1H-NMR: formation and stability of the Fmoc protected active esters were compared. We found that PyBOP is the best choice for successfully coupling both H–β-SAA–OH prototypes. The present comparative results open a reasonable route for building efficiently various –β-SAA– containing homo- and heterooligomers. LA - English DB - MTMT ER - 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 -