α，β聚（N羟丙基氨乙基）DL天冬酰胺COL赖氨酸：作为潜在的非病毒性基因载体的研究.pdf

浙江大学硕士研究生论文 蛋白酶溶液 (1mg/ml)中12小时内就完全降解了。利用MTT方法测PHAAL在 Hela,E.C.V.-304,Bcap37细胞中的细胞毒性，实验结果表明PHAAL的细胞毒性比 聚乙烯亚Hk(Polyethylenimine,PEI(25kD)).聚左旋赖氨酸(Poly-I,-Lysine,PLL(15.7 kD)都要低，而且PHAAL在浓度达到40ug/ml时也没有明显的细胞毒性。利用含 澳乙咙 (0.25mg/ml)的琼脂糖凝胶 (1.0%,w/V)电泳检测PHAAL的DNA结合 能力，发现赖氨酸聚合比例高的PHAAL结合DNA的能力强，其中PHAAL-T25 (DL一天冬氨酸:L一赖氨酸=5:5,mol/mol):DNA=150:1(w/w)时能完全结合DNA, 阻滞其迁移。综合各种实验结果分析，PHAAL是一类可作为非病毒性基因载体的 聚氨基酸类高分子材料。 关键词:热共聚 非病毒性基因载体 聚[DL一天冬氨酸一CO-L一赖氨酸I a，0一聚[(I`I-T=丙基/氨乙基)-DL一天冬酞胺-CO-L-赖氨酸〕 一2一 浙江大学硕士研究生论文 a，0-poly[(N-hydroxypropyl/aminoethyl)-DL-Aspartamide -co-L-Lysinel:potentialnon-viralvectorforgenedelivery MedicinalChemistry CollegeofpharmaceuticalScience,ZhejiangUniversity Postgraduate Yang Zhi Supervisor GupingTang Abstract Polyaminoacidmaterialsarewidelyresearchedasnon-viralgenevectorsbecause oftheadvantages,suchasbiodegradation,lowcytotoxicityandsoon.Polylysine, poly(asparticacid),polyornithineandpolyglutamideofthemareresearchedinalotof articles.Polylysineandpolyornithinehavepositivelychargeinthephysiological conditionandcancondenseDNAbythestaticforce.Poly(asparticacid)hasthe structureoftheimideringandcanbegraftedwiththefunctionalsidechainsof condensingDNAbyring-openingwithalkalinereagents.Accordingtotheadvantages ofmanysitesrecognizedbyenzymesandhigh speedofdegradationof copolyaminoacidmaterials,anewtypeofgenevectormaterial,copolymersofaspartic acidandlysine,issynthesizedbythermalcopolycondensationwithphosphoricacid catalysis.Now thesimilarresearchesarelittle.A seriesofPoly[Aspartic acid-co-L-lysinel(PAL)arecopolycondensedbyDL-asparticeacidandL-lysinewith differentratiosindifferentconditionsandtheirconstructi