Controlled Synthesis and Enzyme-Induced Hydrogelation of Poly(L-phosphotyrosine)s via Ring-Opening Polymerization of α-Amino Acid N-Carboxyanhydride

Tyrosine phosphorylation is an important post-translational modification (PTM) that governs numerous cellular processes. Constructing synthetic phosphotyrosine polypeptides helps expand the horizon of our understanding regarding the fundamental aspects and biological consequences of this PTM. Here, we report the synthesis of a novel monomer, Omicron-diethylphospho L-tyrosine N-carboxyanhydride (pOEt TyrNCA), whose ring-opening polymerization (ROP) mediated by hexamethyldisilazane (HMDS) leads to poly(L- phosphotyrosine) (P(pTyr)) derivatives with controllable molecular weights and narrow molecular-weight distributions. Moreover, P(pTyr)(15)-b-PEG-b-P(pTyr)(15) triblock copolymer (TBP15) undergo sol-gel transition in the presence of alkaline phosphatase. The stiffness of the gel is reinforced by the addition of horseradish peroxidase and hydrogen peroxide. These phosphotyrosine-mimicking polymers are realized for the first time by NCA polymerization and are promising materials for a variety of biological applications.