Issue 8, 2020

A programmable chemical switch based on triggerable Michael acceptors

Abstract

Developing an engineerable chemical reaction that is triggerable for simultaneous chemical bond formation and cleavage by external cues offers tunability and orthogonality which is highly desired in many biological and materials applications. Here, we present a chemical switch that concurrently captures these features in response to chemically and biologically abundant and important cues, viz., thiols and amines. This thiol/amine-triggerable chemical switch is based on a Triggerable Michael Acceptor (TMAc) which bears good leaving groups at its β-position. The acceptor undergoes a “trigger-to-release” process where thiol/amine addition triggers cascaded release of leaving groups and generates a less activated acceptor. The newly generated TMAc can be further reversed to liberate the original thiol/amine by a second nucleophile trigger through a “trigger-to-reverse” process. Within the small molecular volume of the switch, we have shown five locations that can be engineered to achieve tunable “trigger-to-release” kinetics and tailored reversibility. The potential of the engineerable bonding/debonding capability of the chemical switch is demonstrated by applications in cysteine-selective and reversible protein modification, universal self-immolative linkers, and orthogonally addressable hydrogels.

Graphical abstract: A programmable chemical switch based on triggerable Michael acceptors

Supplementary files

Article information

Article type
Edge Article
Submitted
18 Nov 2019
Accepted
10 Jan 2020
First published
10 Jan 2020
This article is Open Access

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

Chem. Sci., 2020,11, 2103-2111

A programmable chemical switch based on triggerable Michael acceptors

J. Zhuang, B. Zhao, X. Meng, J. D. Schiffman, S. L. Perry, R. W. Vachet and S. Thayumanavan, Chem. Sci., 2020, 11, 2103 DOI: 10.1039/C9SC05841A

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements