Reaction Landscape and Bioconjugation Profile of Tyrosinase Generated Quinones
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.