Advanced search
Start date
(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

Full text
Show less -
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: 31

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