Year: 2020
Type: preprint
Abstract: We describe a class of bioconjugation reactions that enables site-specific modification of proteins through enzymatic generation of o-quinone from either tyrosine residues or phenol reagents. The enzymatically generated o-quinone rapidly reacts chemically with numerous common nucleophiles and dienophiles, including thiols, anilines, alkoxyamines, cyclooctynes, and cyclooctenes. Nucleophilic chemoenzymatic reaction with engineered tyrosine residues creates a hydroxytyrosine (HOT) bridge; a similar reaction with phenols creates a hydroxyphenol (HOP). Diels-alder cycloaddition following o-quinone generation results in an arylbicyclodiketone (ABCD). The stability of each conjugate against physiological pH and temperature varies from less than one day to multiple months in vitro.
Source: ChemRxiv
Authors: Patrick Holder, Adel M. ElSohly
Institution: Genentech
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W4250111757