生物催化核苷类化合物修饰好课件.pptVIP

生物催化核苷类化合物修饰 lining@scut.edu.cn 李宁 涉及的反应类型 酰化 脂肪酸酰化 氨酰化 烷氧基羰基化 脱酰化 糖基化 卤代 碱基上的卤代 糖基上的卤代 脱氨化 天然核苷及其类似物 诱变育种 FUdR及其酯生物活性 核苷脂肪酸酯前药 喷昔洛韦[治带状疱疹药]与泛昔洛韦 酶促核苷巴豆酰化 介质工程 疏水性有机溶剂与亲水性有机溶剂混合体系 介质工程 离子液体 PF6，BF4， 介质工程 加入离子液体前体物 介质工程 2-甲基四氢呋喃 是一种THF的可再生的替代品 可以由糠醛转化得到 甘蔗渣及燕麦皮 常用脂肪酶及其优先酰化位点 CAL-B PSL-C 核苷底物识别 核苷底物识别 核苷底物识别 酰基链长专一性 PSL-C 酰基链长专一性 CAL-B TLL 区域选择性翻转 酶促酰化：基团保护 酶促酰化：基团保护 酶促酰化：基团保护 酶促酰化：化合物分离 用于消旋体的拆分 酶促酰化：化合物分离 用于消旋体的拆分 酶促酰化：化合物分离 不成功的例子 酶促酰化：化合物分离 分离呋喃及吡喃核苷 酶促酰化：化合物分离 分离异头碳混合物 酶促酰化：化合物分离 分离异头碳混合物 酶促酰化：化合物分离 分离区域异构体 酶促氨酰化 阿昔洛韦与缬昔洛韦 更昔洛韦与缬更昔洛韦 酶促氨酰化 Moris and Gotor (1994), N-protected amino acid oxime esters, the lipases from Candida antarctica (CAL, SP 435L) and Pseudomonas cepacia (PSL), yields were low to moderate (15-58%) only glycine and β-alanine derivatives were successfully introduced 酶促氨酰化 ChiroCLEC TM BL (cross-linked crystals of subtilisin), 54-63% yields, in acetone-DMF (30%, v/v) ChiroCLEC TM PC (cross-linked crystals of P. cepacia lipase), Amano lipase PS30 (P. cepacia lipase immobilized on Accurel polypropylene), 85% and 81% yields, respectively, on a 20 mg scale 酶促氨酰化 酶促烷氧基羰基化 双前药 were expected to have some synergetic effects and enhanced bioavailability 酶促烷氧基羰基化 酶促烷氧基羰基化 Markovnikov addition Acylation 酶促烷氧基羰基化 Enzymatic Markovnikov addition Acylation 酶促脱酰基化 醇解优于水解 酶促脱酰基化 闭合的三环核苷 寡聚核苷酸已广泛用于疾病的诊断与治疗 酶促水解拆分 2’,3’-二脱氧核苷 潜在的抗HIV药物 酶促脱酰基化 Complete deacylation 酶促脱酰基化 Microbial hydrolysis of acetylated nucleosides a mixture was obtained in most cases Only Cellulomonas cellulans-catalyzed hydrolysis of 2’,3’,5’-tri-O-acetyladenosine and Klebsiella sp.-catalyzed hydrolysis of 2’,3’,5’-tri-O-acetyluridine 5’-hydroxyl free derivatives in 79% and 71% yields, respectively 酶促糖基化 二糖核苷 Compound 110, present in natural tRNA molecules play an important role in the elongation process during protein biosynthesis Compound 111 is a structural element of poly(ADP-ribose) be involved in modulation of the chromatin structure, replication, transcriptio