Expedient Synthesis of Gonadotropin Releasing Hormone (GnRH) Through a Combined Chemical-Enzymatic Approach

Abstract

G onadotropin Releasing Hormone, Enzymatic Peptide Synthesis, Papain, a-Chym otrypsinWe have developed a chemical-enzymatic synthetic approach to gonadotropin releasing hormone G lp '-H is 2-T r p 3-S e r 4-T y r 5-G ly 6-L e u 7-A r g 8-P r o 9-G l y 10-N H 2 (G nR H ) which enables one to perform the synthesis efficiently according to minimal protection strategy with all reactive side chains o f amino acids unprotected. Five peptide bonds H is2-T r p 3, Tyr5-G l y 6, Leu7-A r g 8 and Trp3-S e r 4, S ei^-T yr5 were formed by means o f a-chym otrypsin and papain, respectively. The remaining four bonds G lp '-H is 2, Gly6-L e u 7, Arg8-P r o 9, Pro9-G l y 10 were formed by chemical methods. The synthesis is simple to carry out and there are no problems in scaling up as demonstrated by the final coupling on 2 g scale affording highly pure G nR H in the yield o f 8 4 -9 0 % .