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Site-Selective Modification of Proteins with Oxetanes.

Site-Selective Modification of Proteins with Oxetanes.

Authors :
Boutureira, Omar
Martínez ‐ Sáez, Nuria
Brindle, Kevin M.
Neves, André A.
Corzana, Francisco
Bernardes, Gonçalo J. L.
Source :
Chemistry - A European Journal. 5/11/2017, Vol. 23 Issue 27, p6483-6489. 7p.
Publication Year :
2017

Abstract

Oxetanes are four-membered ring oxygen heterocycles that are advantageously used in medicinal chemistry as modulators of physicochemical properties of small molecules. Herein, we present a simple method for the incorporation of oxetanes into proteins through chemoselective alkylation of cysteine. We demonstrate a broad substrate scope by reacting proteins used as apoptotic markers and in drug formulation, and a therapeutic antibody with a series of 3-oxetane bromides, enabling the identification of novel handles (S-to-S/N rigid, non-aromatic, and soluble linker) and reactivity modes (temporary cysteine protecting group), while maintaining their intrinsic activity. The possibility to conjugate oxetane motifs into full-length proteins has potential to identify novel drug candidates as the next-generation of peptide/protein therapeutics with improved physicochemical and biological properties. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09476539
Volume :
23
Issue :
27
Database :
Academic Search Index
Journal :
Chemistry - A European Journal
Publication Type :
Academic Journal
Accession number :
122988837
Full Text :
https://doi.org/10.1002/chem.201700745