Reaction Landscape and Bioconjugation Profile of Tyrosinase Generated Quinones

Abstract

<p>We describe a class of bioconjugation reactions that</p><p>enables site-specific modification of proteins through</p><p>enzymatic generation of o-quinone from either tyrosine</p><p>residues or phenol reagents. The enzymatically generated</p><p>o-quinone rapidly reacts chemically with numerous</p><p>common nucleophiles and dienophiles, including thiols,</p><p>anilines, alkoxyamines, cyclooctynes, and cyclooctenes.</p><p>Nucleophilic chemoenzymatic reaction with engineered</p><p>tyrosine residues creates a hydroxytyrosine (HOT)</p><p>bridge; a similar reaction with phenols creates a hydroxyphenol</p><p>(HOP). Diels-alder cycloaddition following</p><p>o-quinone generation results in an arylbicyclodiketone (ABCD). The stability of each conjugate against</p><p>physiological pH and temperature varies from less than one day to multiple months in vitro.</p>