Issue 8, 2012

Trimethyl lock: a trigger for molecular release in chemistry, biology, and pharmacology

Abstract

The trimethyl lock is an o-hydroxydihydrocinnamic acid derivative in which unfavorable steric interactions between three pendant methyl groups encourage lactonization to form a hydrocoumarin. This reaction is extremely rapid, even when the electrophile is an amide and the leaving group is an amino group of a small-molecule drug, fluorophore, peptide, or nucleic acid. O-Acylation of the phenolic hydroxyl group prevents reaction, providing a trigger for the reaction. Thus, the release of an amino group from an amide can be coupled to the hydrolysis of a designated ester (or to another chemical reaction that regenerates the hydroxyl group). Trimethyl lock conjugates are easy to synthesize, making the trimethyl lock a highly versatile module for chemical biology and related fields.

Graphical abstract: Trimethyl lock: a trigger for molecular release in chemistry, biology, and pharmacology

Article information

Article type
Perspective
Submitted
29 huhti 2012
Accepted
28 touko 2012
First published
30 touko 2012

Chem. Sci., 2012,3, 2412-2420

Trimethyl lock: a trigger for molecular release in chemistry, biology, and pharmacology

M. N. Levine and R. T. Raines, Chem. Sci., 2012, 3, 2412 DOI: 10.1039/C2SC20536J

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