The preparation and characterization of a new epoxide containing polypeptide, poly(5,6-epoxy-L-norleucine), via postpolymerization modification of poly(L-homoallylglycine) is described. Addition of thiols to the epoxide groups in poly(5,6-epoxy-L-norleucine) was studied as a means to prepare side-chain functional polypeptides. The solution properties of the derivatized polypeptides were studied in water and compared to similar thioether containing functional polypeptides prepared via different routes. Subtle differences in side-chain linkage chemistry were found to influence polypeptide solubility, chain conformation in solution, and thermoresponsive behavior. Poly(5,6-epoxy-L-norleucine) was found to be useful as a readily prepared intermediate that can be reacted with thiols to give a variety of functional polypeptides.