Chemo-enzymatic Synthesis of Z-Asp-Val-Tyr-NH_2——A Precursor Tripeptide of Thymopentin

• 出 处: Chemical Research in Chinese Universities
• 发表日期: 2010年06期
• 关键词: enzymatic thermodynamic catalyze steps hydrolysis solubility stirring hexane car

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%.

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. conditions were pH = 6.5, 40 ° C, thermoase 100 mg, in 2- (N- morpholino) ethanesulfonic acid MES / NaOH (containing 5 mmol / L CaCl2) of n-butanol system in a maximum yield of 27.02%.