Toward Homogeneous Erythropoietin: Application of Metal Free Dethiylation in the Chemical Synthesis of the Ala79-Arg166 Glycopeptide Domain.

We describe herein the assembly of hEPO(79-166), a key glycopeptide segment en route to erythropoietin, in minimally protected form. Key to the success of this synthetic endeavor was the application of our two-step cysteine-free native chemical ligation strategy, by which we achieved formal ligation at alanine and proline residues through the use of an N-terminal amino acid surrogate presenting a readily removable thiol functionality.