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机构地区:[1]中国药科大学生命科学与技术学院,南京210009 [2]四川大学华西药学院,成都610041
出 处:《药物生物技术》2005年第6期401-411,共11页Pharmaceutical Biotechnology
摘 要:治疗性蛋白的分子设计与工程化已取得突破进展,基因工程药物已进入了第三代蛋白质治疗药物发展新阶段。文章重点介绍了蛋白质工程技术在优化蛋白质的疗效、稳定性、靶向性、特异性以及改善免疫原性和药代动力学等方面的分子设计策略,并结合本实验室的研究工作介绍了新近研究成功的蛋白质工程药物类型。对近年来在蛋白质工程药物研究中,常采用的的一些新技术,新方法,如点突变技术、融合蛋白技术、DNA改组技术、分子定向进化技术和蛋白质分子展示技术也作了简要讨论,同时还展望了合理的分子设计与蛋白质工程药物的发展前景。The proteins molecular design is an important method to develop new biotech drugs. The protein engineering technique has become a effective stratagem to improve variant properities of therapeutic proteins,including enhanced thermostability, bioactive specifity, targeted deliverty, decrease in immunity and improving pharmacokinetics. Numerous therapeutic proteins produced by protein engineering has been developed and used in clinic, asparaginase and calcitonin by site directed mutagenesis, PEG- IFN - α2b, γ- pA- Hirudin, propro -GHRH - Gly - Gly - Cys and pro - pro - PTH - Gly - gly has been designed and developed sucessfully in our Lab. Site - directed mutagenesis, DNA suffling, directed evolution, expression of fusion proteins promote the creation of new therpeutic proteins, tends on rational design and engineering of therapeutic proteins were discussed.
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