长效胸腺五肽的合成

Synthesis of site-specific PEGylated thymopentin

目的提高长效胸腺五肽(mPEG(10kD)-TP5)——定位单链聚乙二醇化修饰的胸腺五肽的合成产率。方法选用Fmoc-Tyr(tBu)-Wang树脂和Fmoc/t-Butyl策略完成所有氨基酸的缩合,三氟乙酸对Wang树脂、侧链切割脱除。在碱性条件下,单甲氧基聚乙二醇修饰物(mPEG(10kD)-SPA)定点连接到赖氨酸的侧链氨基(ε-NH2)上。中间产物经钯碳催化氢化,得到mPEG(10kD)-TP5。结果目标产物总收率为20%,新合成路线比我们之前报道的方法产率提高了10倍。结论路线操作简单,易于纯化,产率较高。

Purpose To enhance the yield of site-specific PEGylated（10KD） thymopentin. Methods All the amino acids were step-wise assembled on Fmoc-Tyr（tBu）-wang resin by Fmoc/t-Butyl strategy. Then the Wang resins were cleaved and the side-chains were removed through treatment with trifluoracetic acid. Under alkalescent conditions,the mono-PEGylation was targeted to the ε-amine group of the lysine. The pegylated thymopentin was made by Pd/C catalytic hydrogenation. Results The total yield was 20% , which was improving for 10 times in comparison with the yield reported by us. Conclusion This method is easily handing with high yield and low cost for preparing pegylated TPS.