Reaction Landscape and Bioconjugation Profile of Tyrosinase Generated Quinones

15 May 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


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.


tyrosinase enzyme activity
bioconjugation techniques
Antibody-drug conjugates (ADCs)
protein polymer conjugates
protein chemistry techniques


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.