Jump to main content
Jump to site search

Issue 8, 2012
Previous Article Next Article

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

Author affiliations

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

Back to tab navigation
Please wait while Download options loads

Publication details

The article was received on 29 Apr 2012, accepted on 28 May 2012 and first published on 30 May 2012


Article type: Perspective
DOI: 10.1039/C2SC20536J
Citation: Chem. Sci., 2012,3, 2412-2420
  •   Request permissions

    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

Search articles by author