Human Urotensin-II is an undecapeptide (hUT-II, H-Glu-Thr-Pro-Asp-[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) which was identified as a potent vasoconstrictor that binds with high affinity to UT receptor. The cysteine-linked cyclic region, hUT-II(4-11), is responsible for the biological activity and has been widely used to elucidate the Structure-Activity Relationship of hUT-II. With the aim to investigate the role of hydrogen bond and the effects of a peptide backbone constraint on binding affinity and biological activity, we have designed and synthesized new analogues by multiple N-Methylation of hUT-II(4-11) backbone amide bonds. All the peptides were performed by a novel synthetic approach, in which the introduction of N-methyl groups occur during regular solid-phase peptide synthesis. On these new ligands we evaluated the binding affinity and biological activity at the UT receptor and performed preliminary NMR conformational studies.
DESIGN AND SYNTHESIS OF N-METHYL DERIVATIVES OF UROTENSIN-II / Merlino, Francesco; DI MARO, Salvatore; Yousif, ALI MUNAIM; Campiglia, P.; Meini, S.; Santicioli, P.; Maggi, C. A.; Novellino, Ettore; Grieco, Paolo. - 18:(2012), pp. S199-S200. (Intervento presentato al convegno 32 European Peptide Symposium tenutosi a Atene nel 2-7 settembre 2012) [10.1002/psc.2449].
DESIGN AND SYNTHESIS OF N-METHYL DERIVATIVES OF UROTENSIN-II
MERLINO, FRANCESCOPrimo
;DI MARO, SALVATORE;YOUSIF, ALI MUNAIM;NOVELLINO, ETTORE;GRIECO, PAOLO
2012
Abstract
Human Urotensin-II is an undecapeptide (hUT-II, H-Glu-Thr-Pro-Asp-[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) which was identified as a potent vasoconstrictor that binds with high affinity to UT receptor. The cysteine-linked cyclic region, hUT-II(4-11), is responsible for the biological activity and has been widely used to elucidate the Structure-Activity Relationship of hUT-II. With the aim to investigate the role of hydrogen bond and the effects of a peptide backbone constraint on binding affinity and biological activity, we have designed and synthesized new analogues by multiple N-Methylation of hUT-II(4-11) backbone amide bonds. All the peptides were performed by a novel synthetic approach, in which the introduction of N-methyl groups occur during regular solid-phase peptide synthesis. On these new ligands we evaluated the binding affinity and biological activity at the UT receptor and performed preliminary NMR conformational studies.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
