Tyrosinase-Mediated Bioconjugation. A Versatile Approach to Chimeric Macromolecules

Bioconjug Chem. 2018 Aug 15;29(8):2550-2560. doi: 10.1021/acs.bioconjchem.8b00227. Epub 2018 Jul 19.

Abstract

We present a method for tyrosine-selective and reversible bioconjugation; tyrosines are enzymatically converted into catechols and in situ "clicked" onto boronic acids. Importantly, our process selectively produces catechols and avoids quinones, thereby improving the control over the chemical identity of the products. We have conjugated boronic acid-containing hyaluronic acid (HyA) to peptides bearing tyrosines in variable number and position; the use of tagging peptides for the provision of well exposed tyrosine residues-in our case the hemagglutinin-derived HA-tag-makes our approach applicable to virtually any protein; we have demonstrated this concept by conjugating HA-tagged ovalbumin to HyA, thereby also showing the feasibility of producing chimeric proteoglycans. A caveat of this appproach is that, although the formation of boronic esters does not affect the biological recognition of substrates (ovalbumin and HyA), the introduction of catechols may alter some of their biological properties: for example, only after tyrosinase treatment ovalbumin directly induced dendritic cell maturation, either alone or as a HyA conjugate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boronic Acids / chemistry
  • Catechols / chemistry
  • Feasibility Studies
  • Hyaluronic Acid / chemistry
  • Macromolecular Substances / chemistry*
  • Monophenol Monooxygenase / chemistry*
  • Peptides / chemistry
  • Quinones / chemistry

Substances

  • Boronic Acids
  • Catechols
  • Macromolecular Substances
  • Peptides
  • Quinones
  • Hyaluronic Acid
  • Monophenol Monooxygenase