REDUCTIVE CONVERSION OF N-TERMINAL PYROGLUTAMYL INTO PROLYL RESIDUES IN POLYPEPTIDES AND PROTEINS

The pyrrolidone ring of an N-terminal pyroglutamyl residue in a polypeptide or protein maybe converted, by reduction with diborane in tetrahydrofuran or tetramethylurea, into a pyrrolidine ring. Thus, the originally nonbasic N-terminal residue is identified by its conversion into proline. Although the reduction shows only limited selectivity (carboxyl and peptide groups are partially reduced), yields of proline up to 46% have been obtained in the reduction of an octapeptide analog of gastrin. The generation of N-terminal proline by reduction of native or performic acid oxidized bovine γ-globulin is also observed. Diborane reduction offers a rapid and facile means of demonstrating the presence of an N-terminal residue of pyroglutamic acid and of initiating sequential analysis of the polypeptide chain. © 1969, American Chemical Society. All rights reserved.