胸腺五肽结构修饰进展

Progress in research of the structural modification of thymopentin

胸腺五肽(TP5)由胸腺生成素活性中心的5个氨基酸组成,作为免疫平衡调节剂广泛应用于临床。TP5在体内稳定性差、易被酶解、半衰期极短,导致其所具有的生物活性在临床应用中难以充分发挥。通过结构修饰研发TP5衍生物,提高产物的体内抗酶解能力及生物利用度,更好地发挥其生物活性,是研发新型高效免疫平衡调节剂的重要方向。文中针对TP5进行结构修饰的研究进展,包括氨基酸序列的调整与取代、端基化学修饰与肽键替换、反转类似物及环肽的设计与合成、TP5偶合物的研制等。

Thymopentin （TP5） is constituted with the 5 amino acids at the active center of thymopoietin, and used to treat immune disharmony widely in clinic. TP5 is unstable, can be easily lyzed by enzymes and has short half life in vivo; therefore, its biological activity is obviously reduced. Modification of TP5 structure includes the amino acid replacement and sequence adjustment, the terminal group modification and peptide bond alteration, the retro-inverso analogues, and design and syntheses of cyclic derivatives, and the preparation of TP5 conjugates. The new modified TP5 derivatives possess good stability and strong anti-enzymolysis ability in vivo. This is an important strategy for the research and development of new immunomodulators with higher biological activity.