Biodegradable Polysarcosine with Inserted Alanine Residues: Synthesis and Enzymolysis.

Polysarcosine (PSar), a water-soluble polypeptoid, is gifted with biodegradability via the random ring-opening copolymerization of sarcosine- and alanine--thiocarboxyanhydrides catalyzed by acetic acid in controlled manners. Kinetic investigation reveals the copolymerization behavior of the two monomers. The random copolymers, named PaS, with high molecular weights between 5.3 and 43.6 kg/mol and tunable Ala molar fractions varying from 6 to 43% can be degraded by porcine pancreatic elastase within 50 days under mild conditions (pH = 8.0 at 37 °C). Both the biodegradation rate and water solubility of PaS depend on the content of Ala residues. PaS with Ala fractions below 43% are soluble in water, while the one with 43% Ala self-assembles in water into nanoparticles. Moreover, PaS are noncytotoxic at the concentration of 5 mg/mL. The biodegradability and biocompatibility endow the Ala-containing PSar with the potential to replace poly(ethylene glycol) as a protective shield in drug-delivery.