摘要
目的研究HER-2寡脱氧核苷酸(oligodeoxynucleotides,ODN)与叶酸连接药物的生物学特性。方法 HER-2反义、正义和无义寡脱氧核苷酸与叶酸联接,形成ODN-FA,标记放射性核素锝(99mTc),与新鲜人血浆孵育1．5h、4h和6h,测定血浆蛋白结合率。在新鲜人血清37℃孵育 0．5h、2h、4h和6h,用纸层析法测定血清稳定性。结果 99mTc-ODN-FA的血浆蛋白结合率为反义、正义和无意义寡核苷酸分别为10．58％、12．24％和11．01％;6h血浆蛋白结合率明显升高,分别为 24．45％、23．58％和24．33％,差异具有显著意义(P<0．01)。99mTc-ASODN-FA、99mTc-SODN-FA和 99mTc-NODN-FA 6h放化纯分别为92．20％、92．12％和91．31％,与0．5 h相比略有降低,差异无显著意义。结论 HER-2寡脱氧核苷酸叶酸药物的血浆蛋白结合率6h时为24％,在血清中6h内稳定,能够满足体内外分析的要求。
Objective To study the biology speciality of protooncogene HER-2 oligodeoxynucleotides （ODN） combined with folic acid （FA）. Methods HER-2 antisense oligodeoxynucleotide （ASODN）, sense oligodeoxynucleotide （SODN） and nonsense oligodeoxynucleotide （NODN） were connected with folic acidCFA）, then labeled by ^99mTc forming ^99mTc-ODN-FA which were incubated with fresh human plasma at 37℃ for 1.5, 4 and 6h, determined plasma protein binding percentage. ^99mTc-ODN-FA were incubated with fresh human serum at 37℃ for 0. 5, 2, 4 and 6h, then measured the stability in serum by paper chromatography（PC）. Results The plasma protein binding percentages of ^99mTc-ODN-FA were ASODN 10. 58%, SODN 12. 24%, NODN 11.01% at 1.5h, respectively. The plasma protein binding percentages were evidently increased at 6h compared with 0. 5h which were ASODN 24. 45%, SODN 23. 58%, NODN 24. 33% at 1.5h, respectively （P〈0. 01）. The radiochemical purity （RCP） of ^99mTc-ASODN-FA, ^99mTc-SODN-FA and ^99mTc-NODN-FA were 92. 20%, 92. 12% and 91.31% at 6h, respectively. RCP at 6h were lower than that at 0. 5h, but had no significant difference （P〉0. 05）. Conclusion The biospeciality of HER-2 oligodeoxynucleotides combined with folic acid could satisfy the analysis request in vivo and vitro.
出处
《贵州医药》
CAS
2006年第5期394-396,共3页
Guizhou Medical Journal
基金
贵州省优秀科技教育人才省长专项资金资助项目(编号:黔省专合字(2005)36号)
