# Tyrosinase Cross-Linked PEG Hydrogels with DAT and DATT as Artificial Substrates: Design, Structure, and Functions

## TL;DR

Researchers designed new hydrogels using tyrosinase and artificial substrates, showing potential for biomedical applications due to their controlled release and inert properties.

## Contribution

Identification of DAT and DATT as superior artificial substrates for tyrosinase-catalyzed hydrogel synthesis.

## Key findings

- DAT and DATT were more efficiently converted by tyrosinase than tyrosine.
- Hydrogel properties were tuned by molecular weight, substrate type, and enzyme concentration.
- Hydrogels showed inertness in cell culture and controlled release capabilities.

## Abstract

Enzymes such as oxidases are sustainable tools for hydrogel
synthesis,
but complex competing reactions have limited the mechanistic understanding
and biomedical applications of these materials. Guided by molecular
docking and MM-GBSA calculations, we identified two artificial substrates,
desaminotyrosine (DAT) and desaminotyrosyltyrosine (DATT), that were
experimentally more efficiently converted by mushroom tyrosinase (mTyr)
than the natural substrate tyrosine. These substrates were used to
synthesize hydrogels from DAT/DATT-functionalized star-shaped oligoethylene
glycol (sOEG). Model reactions elucidated the chemical nature and
functionality of the hydrogel netpoints. Material properties were
systematically investigated depending on sOEG molecular weight (5,
10, 20 kDa), substrate type, and mTyr concentration. Functional mesh
sizes and controlled release functions were investigated with fluorescent
dextrans (4–500 kDa) and heparin. Cell culture studies with
L929 fibroblasts and THP-1 monocytes
suggested inertness of the material. These findings provide fundamental
insight into mTyr-catalyzed hydrogel formation and support further
exploration for in situ hydrogel synthesis.