English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/75493
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:


Optimizing the control of apoptosis by amide/triazole isosteric substitution in a constrained peptoid

AuthorsCorredor, Miriam ; Bujons Vilàs, Jordi ; Orzáez, Mar; Sancho, Mónica; Pérez-Payá, Enrique ; Alfonso, Ignacio ; Messeguer Peypoch, Ángel
KeywordsApoptosis inhibitors
Click chemistry
Molecular docking
Issue Date2013
CitationEuropean Journal of Medicinal Chemistry
AbstractApoptosis is a biological process relevant to several human diseases that is strongly regulated through protein–protein complex formation. We have previously reported a peptidomimetic compound as potent apoptotic modulator. Structural studies of this compound showed the presence of cis/trans isomers of the exocyclic tertiary amide bond in slow exchange. This information encouraged us to perform an isosteric replacement of the amide bond by a 1,2,3-triazole moiety, where different substitution patterns would mimic different amide rotamers. The syntheses of these restricted analogs have been carried out using the Ugi multicomponent reaction followed by an intramolecular cyclization. Unexpectedly, for one of the proposed structures, a novel β -lactam compound was formed. All compounds showed to efficiently inhibit apoptosis, in vitro and in cellular extracts, with slight differences for the corresponding regioisomers. We propose the binding to Apaf-1 as the inhibition mechanism.
Publisher version (URL)http://dx.doi.org/10.1016/j.ejmech.2013.03.004
Appears in Collections:(IQAC) Artículos
(IBV) Artículos
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.