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Tyrosinase_Holder-ElSohly_ChemRxiv.pdf (3.65 MB)

Reaction Landscape and Bioconjugation Profile of Tyrosinase Generated Quinones

submitted on 13.05.2020, 05:36 and posted on 15.05.2020, 08:03 by Patrick Holder, Adel M. ElSohly

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.


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Declaration of Conflict of Interest

Patrick Holder and Adel ElSohly are both employees of Genentech