Site-Selective Modification of Proteins with Oxetanes
- Boutureira, O. 13
- Martínez-Sáez, N. 3
- Brindle, K.M. 35
- Neves, A.A. 5
- Corzana, F. 23
- Bernardes, G.J.L. 34
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1
Universitat Rovira i Virgili
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2
Universidad de La Rioja
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3
University of Cambridge
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4
Universidade de Lisboa
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5
Cancer Research UK Cambridge Institute
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Cancer Research UK Cambridge Institute
Cambridge, Reino Unido
ISSN: 0947-6539
Año de publicación: 2017
Volumen: 23
Número: 27
Páginas: 6483-6489
Tipo: Artículo
beta Ver similares en nube de resultadosOtras publicaciones en: Chemistry - A European Journal
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Resumen
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. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.