Methylated mono- and di(ethylene glycol)-functionalized β-sheet forming polypeptides

We have synthesized methylated mono- and di(ethylene glycol)-functionalized polymers of L-serine and L-cysteine that adopt beta -sheet conformations in the solid state: poly(O-(2-(2-methoxyethoxy)ethyl)-L-serine), poly(1); poly(O-(2-(methoxy)ethyl)-L-serine), poly(2); and poly(S-(2-(2-methoxyethoxy)ethoxy)carbonyl- L-cysteine), poly(3). Of these three polymers, only poly(1) was found to be highly soluble in water independent of pH. Circular dichroism analysis of poly(1) in water or trifluoroethanol at 25 degreesC revealed that it is in a random conformation, which was unperturbed by changes in pH, buffer, or temperature. However, addition of methanol or acetonitrile to aqueous solutions of poly(1) resulted in a transition to the beta -sheet conformation, as found in the solid state. The polymers were synthesized by transition metal catalyzed polymerization of amino acid-N-carboxyanhydrides, prepared from the functionalized amino acids and represent a new class of readily processable beta -sheet forming polypeptides.