Affinity-Triggered Assemblies Based on a Designed Peptide-Peptide Affinity Pair.

ABSTRACT

Affinity-triggered assemblies rely on affinity interactions as the driving force to assemble physically crosslinked networks. WW domains are small hydrophobic proteins binding to proline-rich peptides that are typically produced in the insoluble form. Previous works attempted the biological production of the full WW domain in tandem to generate multivalent components for affinity-triggered hydrogels. In this work, an alternative approach is followed by engineering a 13-mer minimal version of the WW domain that retains the ability to bind to target proline-rich peptides. Both ligand and target peptides are produced chemically and conjugated to multivalent polyethylene glycol, yielding two components. Upon mixing together, they form soft biocompatible affinity-triggered assemblies, stable in stem cell culture media, and display mechanical properties in the same order of magnitude as for those hydrogels formed with the full WW protein in tandem.