摘要
目的 :研究结构改造对天花粉蛋白 (TCS)引产活性的影响。方法 :利用定点突变将TCS第 2 19位的天冬酰胺残基改变为半胱氨酸残基 (Q2 19C)以供定点聚乙二醇 (PEG)修饰 ,测定修饰产物的致核糖体失活活性及小鼠中期引产活性。结果 :PEG修饰使TCS的致核糖体失活活性约降低90 % ;相对分子质量为 50 0 0的PEG修饰对引产活性无明显影响 ,而相对分子质量为 2 0 0 0 0的PEG修饰却明显增强引产活性 ;此外 ,PEG修饰使TCS的体内半衰期大为延长。结论 :PEG定点修饰TCS可加强其引产活性 ,原因可能是较长的体内半衰期延长了药物作用的时间。
Aim: To study the effect of structural modification on the abortifacient activity of trichosanthin. Methods: Glutamine residue in 219 of trichosanthin was mutated into cysteine residue (Q219C) by site-directed mutagenesis. The mutein was then modified by polyethylene glycol (PEG). Ribosome-inactivating activity and abortifacient activity of the modified products were determined. Results: Ribosome-inactivating activity was decreased by 90% after PEG modification. There was no significant change in abortifacient activity by 5 000 PEG modification, whereas the activity was significantly enhanced when TCS was modified by 20 000 PEG. Besides, biological half-life of TCS was greatly prolonged by PEG modification. Conclusion: Site-directed PEG modification can enhance the abortifacient activity of TCS, probably due to that prolonged half-life in vivo increases the acting time of the drug. [
出处
《暨南大学学报（自然科学与医学版）》
CAS
CSCD
2000年第4期11-15,共5页
Journal of Jinan University(Natural Science & Medicine Edition)
基金
国家自然科学基金 (395 70 82 2 )
香港研究基金委员会基金 (CUHK374/ 95M)资助项目
关键词
天花粉蛋白
修饰
引产活性
结构改造
引产药物
trichosanthin
site-directed mutagenesis
PEG modification
abortifacient activity
