摘要
目的:研究抗肿瘤转移多聚β肽的聚乙二醇(PEG)化的方法及其作用。方法:采用甲氧基聚乙二醇丙醛(mPEGALD5000)修饰多聚β肽;采用电泳和成像分析系统检测修饰率。以粘附实验检测生物活性。结果:(1)二聚β肽(β2)的修饰率为66.7%,三聚β肽(β3)为52.7%。(2)最佳反应条件为:pH值为5,多聚β肽和mPEGALD5000的摩尔之比为1∶10,反应温度为4℃,反应时间为24h。(3)修饰后产物在4℃下可稳定放置50d。(4)修饰后产物水溶解度增加。(5)β2,β2-PEG,β3和β3-PEG对SMMC-7721和HCCLM6细胞与纤连蛋白(FN)粘附均具有显著的抑制作用(P<0.01),而且PEG修饰后作用显著增强(P<0.05或P<0.01)。结论:采用mPEGALD5000能有效地将多聚β肽PEG化。多聚β肽和PEG修饰物对肿瘤细胞与FN的粘附具有特异的抑制作用,且PEG修饰后作用增强。
AIM：To study the methods of the pegylation of poly beta peptide and its anti-metastasis effect. METHODS： Using methoxy-polyethylene glycol-propylaldehyde （ mPEGALD5000 ） to modify poly-β peptide. The modification rate can be detected by electrophoresis and imaging analysis system. The bioactivity was detected by the adhesion experiment. RESULTS： （1） The modification rate of β dipeptide was 66.7 % by mPEGALD5000, while β tripeptide was 52.7 %. （2） The optimal pH for modification was around 5-6, the optimal molar ratio between poly β2 peptide and mPEGALD5000 was 1： 10. Also, the optimal duration and temperature for the modification was for 24 h at 4 ℃. （3） The product of pegylation can be placed at 4 ℃ for 50 d steadily. （4） The solubility of product was increased greatly. （5） The inhibition of peptides on the adhesion of SMMC-7721 and HCCLM6 hepatoma cells to fibronectin （ FN ） was obvious （ P 〈 0.01 ）. The inhibition effect on the adhesion of pegylated polypeptides was stronger than that of polypeptides （ P 〈 0.05, P 〈 0.01 ）. CONCLUSION ： The mPEGALD5000 can pegylate the poly-beta peptide effectively. The poly-beta peptides and their products of the pegylation can inhibit the adhesion of tumor cells to FN obviously exhibiting more strong inhibition.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2005年第9期723-726,共4页
Chinese Journal of New Drugs and Clinical Remedies
基金
863计划(2004AA215201)
上海市科委重点科技项目(024319212)
关键词
肝肿瘤
肿瘤转移
多聚蛋白质类
聚乙烯二醇类
PEG化
粘附分子
liver neoplasms
neoplasm metastasis
polyproteins
polyethylene glycols
pegylation
adhesion molecule
