Z-Asp-Val-Tyr-NH2,a precursor tripeptide of thymopentin（TP-5）,was successfully synthesized by a combination of chemical and enzyme methods.Firstly,the precursor dipeptide Val-Tyr-NH2 was synthesized by a novel chemical method in four steps including the preparation of NCA-Val,the esterification of L-tyrosine and the ammonolysis of L-tyrosine ethyl ester,and the formation of Val-Tyr-NH2 from NCA-Val and L-Tyr-NH2.Secondly,a thermolysin,thermoase PC 10F was used to catalyze the formation of Z-Asp-Val-Tyr-NH2 in an aqueous/organic solvent diphase system with Z-Asp-OH and Val-Ty-NH2 as the substrates under thermodynamic control.The optimum conditions were pH=6.5,40 ℃,thermoase 100 mg,in 2-（N-morpholino） ethanesulfonic acid MES/NaOH（containing 5 mmol/L CaCl2） of n-butanol system（15/85,volume ratio） for 20 h in a maximum yield of 27.02%.
GUO YiZHANG Yong-xiaJIANG XinZHANG Xue-zhongWU YiXU Li
