TY - JOUR AU - Cseh, Judit AU - Molnár, Gergő Attila AU - Pap, Marianna AU - Laczy, Boglárka AU - Vas, Tibor AU - Kertész, Melinda AU - Németh, Krisztina AU - Hetényi, Csaba AU - Szolomájer-Csikos, Orsolya AU - Tóth, Gábor AU - Reményi, Attila AU - Wittmann, István TI - Incorporation of Oxidized Phenylalanine Derivatives into Insulin Signaling Relevant Proteins May Link Oxidative Stress to Signaling Conditions Underlying Chronic Insulin Resistance JF - BIOMEDICINES J2 - BIOMEDICINES VL - 10 PY - 2022 IS - 5 PG - 24 SN - 2227-9059 DO - 10.3390/biomedicines10050975 UR - https://m2.mtmt.hu/api/publication/32790852 ID - 32790852 N1 - 2nd Department of Medicine and Nephrology-Diabetes Center, University of Pécs Medical School, Pécs, 7624, Hungary Department of Medical Biology and Central Electron Microscopic Laboratory, University of Pécs Medical School, Pécs, 7643, Hungary Signal Transduction Research Group, Szentágothai Research Centre, University of Pécs, Pécs, 7624, Hungary Institute of Organic Chemistry, Research Centre for Natural Sciences, Budapest, 1117, Hungary Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, Pécs, 7643, Hungary Department of Medical Chemistry, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, 6725, Hungary Cited By :3 Export Date: 24 January 2024 Correspondence Address: Wittmann, I.; 2nd Department of Medicine and Nephrology-Diabetes Center, Hungary; email: wittmann.istvan@pte.hu AB - A link between oxidative stress and insulin resistance has been suggested. Hydroxyl free radicals are known to be able to convert phenylalanine (Phe) into the non-physiological tyrosine isoforms ortho- and meta-tyrosine (o-Tyr, m-Tyr). The aim of our study was to examine the role of o-Tyr and m-Tyr in the development of insulin resistance. We found that insulin-induced uptake of glucose was blunted in cultures of 3T3-L1 grown on media containing o- or m-Tyr. We show that these modified amino acids are incorporated into cellular proteins. We focused on insulin receptor substrate 1 (IRS-1), which plays a role in insulin signaling. The activating phosphorylation of IRS-1 was increased by insulin, the effect of which was abolished in cells grown in m-Tyr or o-Tyr media. We found that phosphorylation of m- or o-Tyr containing IRS-1 segments by insulin receptor (IR) kinase was greatly reduced, PTP-1B phosphatase was incapable of dephosphorylating phosphorylated m- or o-Tyr IRS-1 peptides, and the SH2 domains of phosphoinositide 3-kinase (PI3K) bound the o-Tyr IRS-1 peptides with greatly reduced affinity. According to our data, m- or o-Tyr incorporation into IRS-1 modifies its protein–protein interactions with regulating enzymes and effectors, thus IRS-1 eventually loses its capacity to play its role in insulin signaling, leading to insulin resistance. LA - English DB - MTMT ER - TY - JOUR AU - Bagosi, Zsolt AU - Csabafi, Krisztina AU - Balangó, B AU - Pintér, D AU - Szolomájer-Csikos, Orsolya AU - Bozsó, Zsolt AU - Tóth, Gábor AU - Telegdy, Gyula AU - Szabó, Gyula TI - Anxiolytic- and antidepressant-like actions of Urocortin 2 and its fragments in mice JF - BRAIN RESEARCH J2 - BRAIN RES VL - 1680 PY - 2018 SP - 62 EP - 68 PG - 7 SN - 0006-8993 DO - 10.1016/j.brainres.2017.12.011 UR - https://m2.mtmt.hu/api/publication/3310034 ID - 3310034 N1 - Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary Department of Medical Chemistry, Faculty of Medicine, University of Szeged, Hungary Cited By :3 Export Date: 11 October 2023 CODEN: BRREA Correspondence Address: Bagosi, Z.; Department of Pathophysiology, Semmelweis str. 1, Hungary; email: bagosi.zsolt@med.u-szeged.hu LA - English DB - MTMT ER - TY - JOUR AU - Sztojkov-Ivanov, Anita AU - Szolomájer-Csikos, Orsolya AU - Márki, Árpád AU - Tóth, Gábor AU - Zupkó, István TI - Investigation of the pharmacokinetics of the ABCG2 transporter inhibitor Ko134 in mice by a newly developed and validated HPLC method JF - CURRENT PHARMACEUTICAL ANALYSIS J2 - CURR PHARM ANAL VL - 10 PY - 2014 IS - 1 SP - 30 EP - 37 PG - 8 SN - 1573-4129 DO - 10.2174/15734129113099990005 UR - https://m2.mtmt.hu/api/publication/2361026 ID - 2361026 N1 - CAplus AN 2014:423134 (Journal); LA - English DB - MTMT ER - TY - THES AU - Szolomájer-Csikos, Orsolya TI - Módosított peptidek szintézise PB - Szegedi Tudományegyetem (SZTE) PY - 2013 SP - 102 DO - 10.14232/phd.1624 UR - https://m2.mtmt.hu/api/publication/2849975 ID - 2849975 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Szolomájer-Csikos, Orsolya AU - Beery, E AU - Kosa, L AU - Narozsnikné Rajnai, Zsuzsanna AU - Jani, Márton AU - Hetényi, Anasztázia AU - Tauberné Jakab, Katalin AU - Krajcsi, Péter AU - Tóth, Gábor TI - Synthesis and ABCG2 Inhibitory Activity of Novel Fumitremorgin C Analogs - Specificity and Structure Activity Correlations JF - MEDICINAL CHEMISTRY J2 - MED CHEM VL - 9 PY - 2013 IS - 4 SP - 494 EP - 509 PG - 16 SN - 1573-4064 DO - 10.2174/1573406411309040003 UR - https://m2.mtmt.hu/api/publication/2327307 ID - 2327307 N1 - Megjegyzés-23201992 N1 : Chemicals/CASfumitremorgin C, 118974-02-0 Megjegyzés-23201993 N1 : Chemicals/CASfumitremorgin C, 118974-02-0 Megjegyzés-23437218 http://www.ingentaconnect.com/content/ben/mc/2013/00000009/00000004/art00003 Funding Agency and Grant Number: Hungarian grants [TUDAS-1-2006-0029, OMFB-00505/2007, IVDM DQ08, OM-00139/2008, XTTPSRT1, OM-00230/2005, GOP-1.1.1-09/1-2009-0055]\n Funding text: This work was supported by the following Hungarian grants: TUDAS-1-2006-0029, OMFB-00505/2007, IVDM DQ08, OM-00139/2008, XTTPSRT1, OM-00230/2005, GOP-1.1.1-09/1-2009-0055. We thank Dr Zoltan Kele for performing the ESI MS measurements and Ms Timea Rosta for preparation of the manuscript.\n AB - The Ko family of fumitremorgin C analogs are potent and selective ABCG2 inhibitors. However, the most potent Ko compounds carry an ester linkage in their side-chain that makes them chemically and metabolically less stable. We have synthesized 16 tricyclic and 28 tetracyclic novel analogs devoid of ester linkages and tested them for ABCG2 inhibition potency and specificity. Unlike in the tricyclic analog group, potent ABCG2 inhibitory compounds were found among the tetracyclic analogs. The most potent compounds carried the 3S,6S,12aS configuration. We observed a marked stereospecificity as compounds with the 3S,6S,12aS configuration were at least 18-fold more potent inhibitors than their diastereoisomeric pairs with a 3S,6R,12aS configuration. This stereospecificity was not observed in ABCB1 and ABCC1 inhibition. Therefore, a single chiral center confers specificity for ABCG2 over ABCB1 and ABCC1. This is quite unexpected considering the large multivalent drug binding site these transporters harbor. LA - English DB - MTMT ER - TY - JOUR AU - Rovó, Petra AU - Farkas, Viktor AU - Hegyi, Orsolya AU - Szolomájer-Csikos, Orsolya AU - Tóth, Gábor AU - Perczel, András TI - Cooperativity network of Trp-cage miniproteins: probing salt-bridges JF - JOURNAL OF PEPTIDE SCIENCE J2 - J PEPT SCI VL - 17 PY - 2011 IS - 9 SP - 610 EP - 619 PG - 10 SN - 1075-2617 DO - 10.1002/psc.1377 UR - https://m2.mtmt.hu/api/publication/1845947 ID - 1845947 N1 - Megjegyzés-21766115 : FN Thomson Reuters Web of Knowledge WC: Biochemistry & Molecular Biology; Chemistry, Analytical Funding Agency and Grant Number: ICGEB [CRP/HUN08-03]; Hungarian Scientific Research FundOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA K72973, NK67800, NI-68466]; [TAMOP-4.2.1.B-09/1/KMR] Funding text: We are indebted to our colleague Imre Jakli for his crucial contribution to the CCA+ deconvolution studies. This work was supported by grants from ICGEB (CRP/HUN08-03), the Hungarian Scientific Research Fund (OTKA K72973, NK67800 and NI-68466) and TAMOP-4.2.1.B-09/1/KMR. AB - Trp-cage miniprotein was used to investigate the role of a salt-bridge (Asp(9) - Arg(16)) in protein formation, by mutating residues at both sides, we mapped its contribution to overall stability and its role in folding mechanism. We found that both of the above side-chains are also part of a dense interaction network composed of electrostatic, H-bonding, hydrophobic, etc. components. To elucidate the fold stabilizing effects, we compared and contrasted electronic circular dichroism and NMR data of miniproteins equipped with a salt-bridge with those of the salt-bridge deleted mutants. Data were acquired both in neutral and in acidic aqueous solutions to decipher the pH dependency of both fully and partially charged partners. Our results indicate that the folding of Trp-cage miniproteins is more complex than a simple two-state process as we detected an intermediate state that differs significantly from the native fold. The intermediate formation is related to the salt-bridge stabilization; in the miniprotein variants equipped with salt-bridge the population of the intermediate state at acidic pH is significantly higher than it is for the salt-bridge deleted mutants. In this molecular framework Arg(16) stabilizes more than Asp(9) does, because of its higher degree of 3D-fold cooperation. In conclusion, the Xxx(9) <-> Yyy(16) salt-bridge is not an isolated entity of this fold; rather it is an integrated part of a complex interaction network. Copyright (C) 2011 European Peptide Society and John Wiley & Sons, Ltd. LA - English DB - MTMT ER - TY - JOUR AU - Rákosi, Kinga AU - Szolomájer-Csikos, Orsolya AU - Kalmár, László AU - Szurmai, Zoltán AU - Kerékgyártó, János AU - Tóth, Gábor TI - Synthesis of N-glycopeptides applying glycoamino acid building blocks with a combined Fmoc/Boc strategy JF - PROTEIN AND PEPTIDE LETTERS J2 - PROTEIN PEPTIDE LETT VL - 18 PY - 2011 IS - 7 SP - 679 EP - 683 PG - 5 SN - 0929-8665 DO - 10.2174/092986611795446003 UR - https://m2.mtmt.hu/api/publication/1837159 ID - 1837159 N1 - Megjegyzés-21977559 Z9: 1 WC: Biochemistry & Molecular Biology LA - English DB - MTMT ER - TY - CHAP AU - Szolomájer-Csikos, Orsolya AU - Rákosi, Kinga AU - Hegyi, Orsolya AU - Kalmár, László AU - Kerékgyártó, János AU - Tóth, Gábor ED - Lebl, M ED - Meldal, M ED - Jensen, KJ ED - Hoeg-Jensen, T TI - The application of the new tTin(IV) chloride deprotection for the preparation of glycosylated peptides T2 - Peptides 2010, Tales of peptides: Proceedings of the thirthy-first European Peptide Symposium PB - European Peptide Society CY - Prato SN - 9780971556058 PY - 2010 SP - 98 EP - 99 PG - 2 UR - https://m2.mtmt.hu/api/publication/1945061 ID - 1945061 LA - English DB - MTMT ER - TY - CHAP AU - Tóth, Gábor AU - Rákosi, Kinga AU - Hegyi, Orsolya AU - Szolomájer-Csikos, Orsolya AU - Kalmár, L AU - Kerékgyártó, János ED - Lankinen, H TI - Glycopeptides “C a synthetic challenge. T2 - Peptides 2008: Chemistry of Peptides in Life Science, Technology and Medicine PB - Finnish Peptide Society CY - Helsinki SN - 9789529276974 PY - 2008 SP - 148 EP - 149 PG - 2 UR - https://m2.mtmt.hu/api/publication/1945051 ID - 1945051 LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Gábor AU - Rákosi, Kinga AU - Hegyi, Orsolya AU - Szolomájer-Csikos, Orsolya AU - Kalmár, László AU - Kerékgyártó, János TI - Glycopeptides - a synthetic challenge JF - JOURNAL OF PEPTIDE SCIENCE J2 - J PEPT SCI VL - 14 PY - 2008 IS - 8 SP - 71 EP - 72 PG - 2 SN - 1075-2617 UR - https://m2.mtmt.hu/api/publication/1474490 ID - 1474490 N1 - SU: Suppl. S LA - English DB - MTMT ER -