Design, synthesis, conformational analysis, and biological activity of Cα1-to-Cα6 1,4- and 4,1-disubstituted 1H-[1,2,3]triazol-1-yl-bridged oxytocin analogues.

Bibliographic Details
Title:	Design, synthesis, conformational analysis, and biological activity of Cα¹-to-Cα⁶ 1,4- and 4,1-disubstituted 1H-[1,2,3]triazol-1-yl-bridged oxytocin analogues.
Authors:	Nuti, Francesca¹ (AUTHOR), Larregola, Maud² (AUTHOR), Staśkiewicz, Agnieszka^1,3 (AUTHOR), Retzl, Bernhard⁴ (AUTHOR), Tomašević, Nataša⁴ (AUTHOR), Macchia, Lorenzo¹ (AUTHOR), Street, Maria E.⁵ (AUTHOR), Jewgiński, Michał³ (AUTHOR), Lequin, Olivier⁶ (AUTHOR), Latajka, Rafal³ (AUTHOR), Rovero, Paolo⁷ (AUTHOR), Gruber, Christian W.⁴ (AUTHOR), Chorev, Michael⁸ (AUTHOR), Papini, Anna Maria¹ (AUTHOR) annamaria.papini@unifi.it
Superior Title:	Journal of Enzyme Inhibition & Medicinal Chemistry. Dec2023, Vol. 38 Issue 1, p1-15. 15p.
Subject Terms:	OXYTOCIN, PEPTIDES, CONFORMATIONAL analysis, MOIETIES (Chemistry), *PHARMACOKINETICS
Abstract:	Oxytocin (OT) is a neurohypophyseal peptide hormone containing a disulphide-bridged pseudocyclic conformation. The biomedical use of OT peptides is limited amongst others by disadvantageous pharmacokinetic parameters. To increase the stability of OT by replacing the disulphide bridge with the stable and more rigid [1,2,3]triazol-1-yl moiety, we employed the Cu2+-catalysed side chain-to-side chain azide-alkyne 1,3-cycloaddition. Here we report the design, synthesis, conformational analysis, and in vitro pharmacological activity of a homologous series of Cα1-to-Cα6 side chain-to-side chain [1,2,3]triazol-1-yl-containing OT analogues differing in the length of the bridge, location, and orientation of the linking moiety. Exploiting this macrocyclisation approach, it was possible to generate a systematic series of compounds providing interesting insight into the structure-conformation-function relationship of OT. Most analogues were able to adopt similar conformation to endogenous OT in water, namely, a type I β-turn. This approach may in the future generate stabilised pharmacological peptide tools to advance understanding of OT physiology. [ABSTRACT FROM AUTHOR]
	Copyright of Journal of Enzyme Inhibition & Medicinal Chemistry is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database:	Academic Search Premier
Full text is not displayed to guests.	Login for full access.

Description
Description not available.