Tyrosinase-Mediated Bioconjugation. A Versatile Approach to Chimeric Macromolecules

Area of Science:

• Bioconjugation Chemistry
• Biomaterials Science
• Proteomics

Background:

• Tyrosine residues are common in proteins but challenging to selectively modify.
• Existing bioconjugation methods may lack control over product identity or biological activity.
• Developing methods for controlled protein modification is crucial for biomaterial development.

Purpose of the Study:

• To develop a tyrosine-selective and reversible bioconjugation method.
• To enable the creation of novel protein-hyaluronic acid (HyA) conjugates.
• To investigate the impact of catechol modification on protein biological activity.

Main Methods:

• Enzymatic conversion of tyrosine residues to catechols.
• In situ click chemistry conjugation of catechols with boronic acids.
• Conjugation of hyaluronic acid (HyA) to tyrosine-containing peptides and proteins (ovalbumin).

Main Results:

• Achieved selective catechol formation, avoiding quinones for better product control.
• Successfully conjugated HyA to HA-tagged peptides and ovalbumin, forming chimeric proteoglycans.
• Demonstrated that boronic ester formation did not affect biological recognition of ovalbumin and HyA.
• Observed altered biological properties, such as direct induction of dendritic cell maturation by tyrosinase-treated ovalbumin conjugates.

Conclusions:

• The developed method offers precise control over tyrosine-selective bioconjugation.
• This approach facilitates the creation of functional chimeric proteoglycans.
• Catechol introduction can modulate protein biological functions, requiring further investigation.