Conformational determination of potent antagonistic analogues of oxytocin by nuclear magnetic resonance spectroscopy and molecular dynamics simulations

0457049 - ÚOCHB 2016 BG eng C - Konferenční příspěvek (zahraniční konf.)
Magafa, V. - Kritsi, E. - Potamitis, C. - Zoumpoulakis, P. - Assimomytis, N. L. - Borovičková, Lenka - Slaninová, Jiřina - Cordopatis, P.
Conformational determination of potent antagonistic analogues of oxytocin by nuclear magnetic resonance spectroscopy and molecular dynamics simulations.
Peptides 2014. Proceedings of the Thirty-Third European Peptide Symposium. Sofia: Bulgarian Peptide Society, 2015 - (Naydenova, E.; Pajpanova, T.; Danalev, D.), s. 198-199. ISBN 978-619-90427-2-4.
[Peptides 2014. European Peptide Symposium /33./. Sofia (BG), 31.08.2014-05.09.2014]
Institucionální podpora: RVO:61388963
Klíčová slova: oxytocin * NMR spectroscopy * molecular dynamics simulations
Kód oboru RIV: CE - Biochemie
http://bulpepsoc.info/wp-content/uploads/2015/06/PEPTIDES-2014-electronic-version.pdf

The neurohypophysial hormone, oxytocin (OT) is a cyclic nonapeptide [cyclo(Cys1-Tyr2-Ile3-Gln4-Asn5-Cys6)-Pro7-Leu8-Gly9-NH2], with important biological properties. The widespread allocation of OT receptors (OTR) in the central nervous system has firmly established OT as a central neurotransmitter with roles in reproductive and social behaviors. Also, a new role of OT has been identified in the pathology of cancer [1]. Deamino+oxytocin analogues containing D-aromatic acids in position 2 and non natural amino acids in position 3, were synthesized and their biological activities were tested. Towards this direction, conformational studies of OT, [Mpa1, D-1-Nal2, L-Thi3]OT (1), [Mpa1, D-Tyr(Et)2, L-Thi3]OT (2), and [Mpa1, D-Tyr(Et)2, D-Thi3]OT (3) analogues were performed. Biological evaluation of studied OT analogues as compared to the native hormone, revealed that both analogues 1(pA2=8.50±0.24) and 2 (pA2=7.09±0.13) exhibit antagonistic action at uterine receptor, while the analogue 3 is inactive. In the present study, the crucial conformational features, possibly responsible for the antagonistic activity, were determined by combining NMR spectroscopy and Molecular Dynamic Simulations.
Trvalý link: http://hdl.handle.net/11104/0257492