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Tyrosinase_Holder-ElSohly_ChemRxiv.pdf (3.65 MB)
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Reaction Landscape and Bioconjugation Profile of Tyrosinase Generated Quinones

preprint
submitted on 13.05.2020 and posted on 15.05.2020 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.

History

Email Address of Submitting Author

holderp@gene.com

Institution

Genentech

Country

USA

ORCID For Submitting Author

0000-0003-0971-191X

Declaration of Conflict of Interest

Patrick Holder and Adel ElSohly are both employees of Genentech

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