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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Stoichiometric and irreversible cysteine-selective protein modification using carbonylacrylic reagents

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Author(s):
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Bernardim, Barbara ; Cal, Pedro M. S. D. ; Matos, Maria J. ; Oliveira, Bruno L. ; Martinez-Saez, Nuria ; Albuquerque, Ines S. ; Perkins, Elizabeth ; Corzana, Francisco ; Burtoloso, Antonio C. B. ; Jimenez-Oses, Gonzalo ; Bernardes, Goncalo J. L.
Total Authors: 11
Document type: Journal article
Source: NATURE COMMUNICATIONS; v. 7, OCT 26 2016.
Web of Science Citations: 43
Abstract

Maleimides remain the reagents of choice for the preparation of therapeutic and imaging protein conjugates despite the known instability of the resulting products that undergo thiol-exchange reactions in vivo. Here we present the rational design of carbonylacrylic reagents for chemoselective cysteine bioconjugation. These reagents undergo rapid thiol Michael-addition under biocompatible conditions in stoichiometric amounts. When using carbonylacrylic reagents equipped with PEG or fluorophore moieties, this method enables access to protein and antibody conjugates precisely modified at pre-determined sites. Importantly, the conjugates formed are resistant to degradation in plasma and are biologically functional, as demonstrated by the selective imaging and detection of apoptotic and HER2+ cells, respectively. The straightforward preparation, stoichiometric use and exquisite cysteine selectivity of the carbonylacrylic reagents combined with the stability of the products and the availability of biologically relevant cysteine-tagged proteins make this method suitable for the routine preparation of chemically defined conjugates for in vivo applications. (AU)

FAPESP's process: 12/22274-2 - Study in the photochemical Wolff rearrangement from a,b-unsaturated diazoketones. aplication in diversity synthesis of nitrogen and oxygen heterocycles
Grantee:Barbara Bernardim de Souza
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/25504-1 - Development of new methodologies for the asymmetric a-functionalization of carbonyl compounds using chiral catalysts
Grantee:Antonio Carlos Bender Burtoloso
Support type: Regular Research Grants
FAPESP's process: 15/07509-1 - Site-specific modification of proteins via aqueous Horner-Wadsworth-Emmons reaction followed by Wolff rearrangement
Grantee:Barbara Bernardim de Souza
Support type: Scholarships abroad - Research Internship - Doctorate