N-Carboxy-α-amino acid anhydrides readily undergo polymerization, with carbon dioxide evolution, to yield the corresponding poly-α-amino acid. The study of a polypeptidyl enzyme may also help to elucidate the role played by ɛ-amino groups in the unmodified enzyme. In this context the effects of the modification is studied with regard to the catalytic activity, the physical and chemical properties, as well as the immunological reactivity of the enzyme. The polymerization on proteins proceeds under mild conditions (aqueous media, low temperature, and neutral pH range), which do not, as a rule, cause denaturation of most proteins. A considerable number of polypeptidyl enzymes have been prepared. These often retain enzymatic activity, although differing markedly from the native protein in their physicochemical properties, such as solubility and electrophoretic mobility. The investigation of a series of polypeptidyl derivatives of a given enzyme may shed light on the effect of charge, steric hindrance, and hydrophilic and hydrophobie groups on the catalytic activity of the enzyme. In studies of the conformation of an enzyme molecule and its relationship to enzymatic activity, reactions are often used which cause insolubilization of the products obtained.