Chemo-enzymatic Synthesis of Z-Asp-Val-Tyr-NH2―A Precursor Tripeptide of Thymopentin

Chemical Research in Chinese Universities ›› 2010, Vol. 26 ›› Issue (6): 942-947.

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Chemo-enzymatic Synthesis of Z-Asp-Val-Tyr-NH2―A Precursor Tripeptide of Thymopentin

GUO Yi¹, ZHANG Yong-xia¹, JIANG Xin¹, ZHANG Xue-zhong¹, WU Yi^2* and XU Li^1*

1. Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, Jilin University, Changchun 130012, P. R. China;
2. College of Pharmacy, Jilin University, Changchun 130021, P. R. China

Received:2010-09-29 Revised:2010-10-25 Online:2010-11-25 Published:2010-12-01
Contact: XU Li;WU Yi E-mail:xuli@jlu.edu.cn;wuyi@jlu.edu.cn
About author:XU Li and WU Yi. E-mail: xuli@jlu.edu.cn; wuyi@jlu.edu.cn
Supported by:
Supported by the National High Technology Research and Development Program of China(No.2008AA10Z321) and the Social Development Project of Science and Technology Department of Jilin Province, China(Nos.200805133 and 20090133).

Abstract

Abstract: 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 °C, 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%.

Key words: Thymopentin, Peptide synthesis, Thermoase, Organic solvent

GUO Yi, ZHANG Yong-xia, JIANG Xin, ZHANG Xue-zhong, WU Yi* and XU Li*. Chemo-enzymatic Synthesis of Z-Asp-Val-Tyr-NH2―A Precursor Tripeptide of Thymopentin[J]. Chemical Research in Chinese Universities, 2010, 26(6): 942-947.

References

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Chemo-enzymatic Synthesis of Z-Asp-Val-Tyr-NH2―A Precursor Tripeptide of Thymopentin

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