中国生化药物杂志
中國生化藥物雜誌
중국생화약물잡지
Chinese Journal of Biochemical Pharmaceutics
2015年
9期
1-3,7
,共4页
高红林%韩京华%杨翠红%刘雅洁%宋娜玲%王燕铭
高紅林%韓京華%楊翠紅%劉雅潔%宋娜玲%王燕銘
고홍림%한경화%양취홍%류아길%송나령%왕연명
聚天冬酰胺衍生物%炔基化%药物载体%生物相容性
聚天鼕酰胺衍生物%炔基化%藥物載體%生物相容性
취천동선알연생물%결기화%약물재체%생물상용성
derivatives of polyasparamide%ethynylation%drug carrier%biocompatibility
目的:合成一种新的炔基化聚天冬酰胺-g-苯丙氨酸衍生物用作功能化药物载体。方法以L-苯丙氨酸为原料制备苯丙氨酸甲酯盐酸盐,对聚琥珀酰亚胺( polyasparamide, PSI)进行开环反应得到聚天冬酰胺-g-苯丙氨酸衍生物PSI-Phe-OMe,使用炔丙胺进一步开环得到炔基化的聚天冬酰胺-g-苯丙氨酸衍生物PSI-Phe-OMe-PA;通过1 HNMR进行聚合物结构确证;通过MTT法、显微观察法和碘化丙啶( PI)染色法等确定PSI-Phe-OMe-PA对细胞增殖、形态以及细胞周期的影响。结果1 HNMR确证了PSI-Phe-OMe-PA的分子结构,苯丙氨酸甲酯盐酸盐对PSI的开环率为40%,炔丙胺进一步开环后可使开环率接近100%;MTT实验表明PSI-Phe-OMe-PA对NIH 3T3和HepG22种细胞的毒性较小,在浓度为100μg/mL时细胞存活率仍在80%左右,且对细胞形貌和细胞周期无显著影响。结论苯丙氨酸甲酯和炔丙胺可依次对聚琥珀酰亚胺进行开环合成炔基化的聚天冬酰胺开环衍生物PSI-Phe-OMe-PA,且PSI-Phe-OMe-PA是一类安全的功能化药物载体。
目的:閤成一種新的炔基化聚天鼕酰胺-g-苯丙氨痠衍生物用作功能化藥物載體。方法以L-苯丙氨痠為原料製備苯丙氨痠甲酯鹽痠鹽,對聚琥珀酰亞胺( polyasparamide, PSI)進行開環反應得到聚天鼕酰胺-g-苯丙氨痠衍生物PSI-Phe-OMe,使用炔丙胺進一步開環得到炔基化的聚天鼕酰胺-g-苯丙氨痠衍生物PSI-Phe-OMe-PA;通過1 HNMR進行聚閤物結構確證;通過MTT法、顯微觀察法和碘化丙啶( PI)染色法等確定PSI-Phe-OMe-PA對細胞增殖、形態以及細胞週期的影響。結果1 HNMR確證瞭PSI-Phe-OMe-PA的分子結構,苯丙氨痠甲酯鹽痠鹽對PSI的開環率為40%,炔丙胺進一步開環後可使開環率接近100%;MTT實驗錶明PSI-Phe-OMe-PA對NIH 3T3和HepG22種細胞的毒性較小,在濃度為100μg/mL時細胞存活率仍在80%左右,且對細胞形貌和細胞週期無顯著影響。結論苯丙氨痠甲酯和炔丙胺可依次對聚琥珀酰亞胺進行開環閤成炔基化的聚天鼕酰胺開環衍生物PSI-Phe-OMe-PA,且PSI-Phe-OMe-PA是一類安全的功能化藥物載體。
목적:합성일충신적결기화취천동선알-g-분병안산연생물용작공능화약물재체。방법이L-분병안산위원료제비분병안산갑지염산염,대취호박선아알( polyasparamide, PSI)진행개배반응득도취천동선알-g-분병안산연생물PSI-Phe-OMe,사용결병알진일보개배득도결기화적취천동선알-g-분병안산연생물PSI-Phe-OMe-PA;통과1 HNMR진행취합물결구학증;통과MTT법、현미관찰법화전화병정( PI)염색법등학정PSI-Phe-OMe-PA대세포증식、형태이급세포주기적영향。결과1 HNMR학증료PSI-Phe-OMe-PA적분자결구,분병안산갑지염산염대PSI적개배솔위40%,결병알진일보개배후가사개배솔접근100%;MTT실험표명PSI-Phe-OMe-PA대NIH 3T3화HepG22충세포적독성교소,재농도위100μg/mL시세포존활솔잉재80%좌우,차대세포형모화세포주기무현저영향。결론분병안산갑지화결병알가의차대취호박선아알진행개배합성결기화적취천동선알개배연생물PSI-Phe-OMe-PA,차PSI-Phe-OMe-PA시일류안전적공능화약물재체。
Objective To synthesize a new ethynylated open ring derivatives of polyasparamide as functional drug carrier.Methods L-phenylalanine methyl ester hydrochloride was prepared using L-phenylalanine and then was used for ring opening reaction of polysuccinimide.To synthesize the target product of PSI-Phe-OMe-PA, the obtained polyasparamide-g-phenylalanine derivatives ( PSI-Phe-OMe) was further ring opened by propargylamine.The structure of PSI-Phe-OMe-PA was confirmed by 1 H NMR.The biocompatibility of PSI-Phe-OMe-PA was evaluated by MTT method, inverted microscope observation and cell cycles analysis ( propidium iodide staining ) .Results The ring-opening rate of polyasparamide by L-phenylalanine methyl ester and propargylamine was 40%and 100%, respectively.All results of biocompatibility studies indicated that PSI-Phe-OMe-PA may be a good candidate for functional drug carrier.Conclusion Based on the ring-opening capability of amino-group and the specificity of click reaction, L-phenylalanine methyl ester hydrochloride and propargylamine were used successively to react with polyasparamide.PSI-Phe-OMe-PA is a biocompatible functional drug carrier.