Polysarcosine (PSar), a water-soluble polypeptoid, is gifted with biodegradability via random ring-opening copolymerization of sarcosine- and alanine-N-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 22.0 and 43.6 kg/mol and tunable Ala molar fractions varying from 6% to 43% are able to be degraded by porcine pancreatic

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... ase within 50 days in 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 non-cytotoxic at the concentration of 5 mg/mL. The biodegradability and biocompatibility endow the Ala-containing PSar with potential to replace PEG as protective shield in drug-delivery.