An efficient chemical-enzymatic synthesis of LHRH N-terminal pentapeptide.

Abstract

Synthesis of LHRH N-terminal pentapeptide Glp1-His2-Trp3-Ser4-Tyr5-OMe (6) involving 3 + 2 enzymatic coupling has been developed. Synthetic strategy features the formation of one peptide bond (Glp-His) by chemical coupling and three peptide bonds by means of papain (Trp-Ser, Ser-Tyr) or alpha-chymotrypsin (His-Trp). High efficiency of this six-step synthesis is demonstrated by 44% overall yield. Its advantages are the use of inexpensive enzymes, simple isolation of intermediates and final pentapeptide, and easy recovery of substrates.