Issue 7, 2016

Fast and selective labeling of N-terminal cysteines at neutral pH via thiazolidino boronate formation

Abstract

Facile labeling of proteins of interest is highly desirable in proteomic research as well as in the development of protein therapeutics. Herein we report a novel method that allows for fast and selective labeling of proteins with an N-terminal cysteine. Although N-terminal cysteines are well known to conjugate with aldehydes to give thiazolidines, the reaction requires acidic conditions and suffers from slow kinetics. We show that benzaldehyde with an ortho-boronic acid substituent readily reacts with N-terminal cysteines at neutral pH, giving rate constants on the order of 103 M−1 s−1. The product features a thiazolidino boronate (TzB) structure and exhibits improved stability due to formation of the B–N dative bond. While stable at neutral pH, the TzB complex dissociates upon mild acidification. These characteristics make the TzB conjugation chemistry potentially useful for the development of drug–protein conjugates that release the small molecule drug in acidic endosomes.

Graphical abstract: Fast and selective labeling of N-terminal cysteines at neutral pH via thiazolidino boronate formation

Supplementary files

Article information

Article type
Edge Article
Submitted
13 Jan 2016
Accepted
04 Apr 2016
First published
04 Apr 2016
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2016,7, 4589-4593

Fast and selective labeling of N-terminal cysteines at neutral pH via thiazolidino boronate formation

A. Bandyopadhyay, S. Cambray and J. Gao, Chem. Sci., 2016, 7, 4589 DOI: 10.1039/C6SC00172F

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