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
Primo
;
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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/597925
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