Issue 2, 2016

Photochemically re-bridging disulfide bonds and the discovery of a thiomaleimide mediated photodecarboxylation of C-terminal cysteines

Abstract

Described in this work is a novel method for photochemically manipulating peptides and proteins via the installation of cysteine-selective photoactive tags. Thiomaleimides, generated simply by the addition of bromomaleimides to reduced disulfide bonds, undergo [2 + 2] photocycloadditions to reconnect the crosslink between the two cysteine residues. This methodology is demonstrated to enable photoactivation of a peptide by macrocyclisation, and reconnection of the heavy and light chains in an antibody fragment to form thiol stable conjugates. Finally we report on an intriguing thiomaleimide mediated photochemical decarboxylation of C-terminal cysteines, discovered during this study.

Graphical abstract: Photochemically re-bridging disulfide bonds and the discovery of a thiomaleimide mediated photodecarboxylation of C-terminal cysteines

Supplementary files

Article information

Article type
Communication
Submitted
13 Oct 2015
Accepted
16 Nov 2015
First published
25 Nov 2015
This article is Open Access
Creative Commons BY license

Org. Biomol. Chem., 2016,14, 455-459

Author version available

Photochemically re-bridging disulfide bonds and the discovery of a thiomaleimide mediated photodecarboxylation of C-terminal cysteines

D. A. Richards, S. A. Fletcher, M. Nobles, H. Kossen, L. Tedaldi, V. Chudasama, A. Tinker and J. R. Baker, Org. Biomol. Chem., 2016, 14, 455 DOI: 10.1039/C5OB02120K

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements