Functionalized Double Strain-Promoted Stapled Peptides for Inhibiting the p53-MDM2 Interaction.


Journal

ACS omega
ISSN: 2470-1343
Titre abrégé: ACS Omega
Pays: United States
ID NLM: 101691658

Informations de publication

Date de publication:
21 Jan 2020
Historique:
received: 17 10 2019
accepted: 24 12 2019
entrez: 28 1 2020
pubmed: 28 1 2020
medline: 28 1 2020
Statut: epublish

Résumé

The Sondheimer dialkyne reagent has previously been employed in strain-promoted double-click cycloadditions with bis-azide peptides to generate stapled peptide inhibitors of protein-protein interactions. The substituted variants of the Sondheimer dialkyne can be used to generate functionalized stapled peptide inhibitors with improved biological properties; however, this remains a relatively underdeveloped field. Herein, we report the synthesis of new substituted variants of Sondheimer dialkyne and their application in the stapling of p53-based diazido peptides to generate potent stapled peptide-based inhibitors of the oncogenic p53-MDM2 interaction. The functionalized stapled peptide formed from a

Identifiants

pubmed: 31984273
doi: 10.1021/acsomega.9b03459
pmc: PMC6977200
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1157-1169

Informations de copyright

Copyright © 2020 American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

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Auteurs

Krishna Sharma (K)

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.

Alexander V Strizhak (AV)

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.

Elaine Fowler (E)

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.

Wenshu Xu (W)

Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.

Ben Chappell (B)

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.

Hannah F Sore (HF)

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.

Warren R J D Galloway (WRJD)

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.

Matthew N Grayson (MN)

Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, U.K.

Yu Heng Lau (YH)

School of Chemistry, The University of Sydney, Eastern Avenue, Sydney, New South Wales 2006, Australia.

Laura S Itzhaki (LS)

Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.

David R Spring (DR)

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.

Classifications MeSH