酪丝缬肽的结构修饰及其稳定性和安全性的初步评价

Structural Modification of Tyroservatide and the Prelimary Evaluation of Their Stability and Safety

通过固相多肽法成功合成了酪丝缬肽(YSV)以及其结构修饰物(Z-GP-YSV-NH2),总收率分别为45.3%和52.3%。分别研究了YSV和Z-GP-YSV-NH2在PBS缓冲液、DMEM培养基和大鼠血浆中的稳定性,发现两者在PBS和DMEM中都很稳定,但YSV在大鼠血浆中温浴2 h后基本降解完全;而Z-GP-YSV-NH2温浴12h后只降解67%。还评价了YSV和Z-GP-YSV-NH2对人胚肾细胞293的细胞毒性,发现两者的细胞毒性都很低。当剂量为200μg/mL时,其增殖抑制率分别为20%和10.3%。

Tyroservatide （YSV） and its structural modification （Z-GP-YSV-NH2） were successfully synthesized by solidphase peptide synthesis. The overall yields were 45.3% and 52.3% respectively. The stabilities of YSY and Z-GP-YSV-NH2 in PBS buffer, DMEM culture and rat blood plasma were also investigated in this study. It was found that both YSV and Z-GP-YSV-NH2 were stable in either PBS or DMEM medium. However, YSV was completely degraded after bathing in rat blood plasma for 2 h; while only 67% of Z-GP-YSV-NH2 was degraded after 12-hours bath. In current paper, the cytotoxicities of YSV and Z-GP-YSV-NH2 to human renal cell 293 were also evaluated. It was displayed that the cytotoxicities of both compounds were very low, in which the growth inhibition rate were 20% and 10.3% respectively when the dosages were 200 μg/mL.