Reduction of methionine sulfoxide in peptide synthesis by use of 2-mercaptopyridine in liquid hydrogen fluoride.

Abstract

Methionine d-sulfoxide can be reduced to methionine in liquid hydrogen fluoride in the presence of 2-mercaptopyridine. The utility of the reaction in peptide synthesis was demonstrated by preparation of the model peptide H-Leu-Gly-Arg-Leu-Gly-Met-Phe-OH (I) by the solid-phase method. When the peptide resin H-Leu-Gly-Arg(Tos)-Leu-Gly-Met(d-sulfoxide)-Phe-resin is treated in liquid HF in the presence of the standard scavenger anisole, H-Leu-Gly-Arg-Leu-Gly-Met(d-sulfoxide)-Phe-OH (II) is obtained in ca. 66% overall yield with no detectable trace of I. When the same peptide resin is treated in like manner in the added presence of 2-mercaptopyridine, I is obtained in ca. 63% overall yield with no detectable trace of II.