烷基化试剂课件.ppt

5-FdUMP binds to thymidylate synthetase to give an intermediate that resembles the intermediate formed with uridylic acid, however, this intermediate cannot break down and the enzyme is inhibited 胸腺嘧啶脱氧核甙酸合成酶 Metabolism of 5-fluorouracil Synthesis of 5-FU base Ring open product Stability in NaHSO3 （二） Cytarabine （ARA-C,阿糖胞苷） Pyrimidine antimetabolite in which sugar is modified 胞嘧啶衍生物 胞嘧啶 阿拉伯糖 The normal 2’ configuration is α 主要用于治疗急性粒细胞白血病 Metabolic activation and inactivation of ARA-C 阿糖胞苷在体内的代谢激活与失活 Inactive species Mechanism of Action for ARA-C ARA-CTP inhibits the conversion of cytidylic acid to 2’-deoxycytidylic acid ARA-CTP 抑制磷酸胞苷转换为脱氧磷酸胞苷 ARA-CTP also inhibits DNA-dependent DNA polymerase 抑制依赖DNA的DNA多聚酶 ARA-C causes miscoding after being incorporated into DNA 掺入DNA后编码错误，DNA合成终止 Cancer Therapy The specific approach used to treat cancer depends upon the specific type, location, and stage of the cancer Fundamental techniques available to treat cancer: Surgery Radiation therapy Immunologic treatment Chemical based approaches Generally, each has its own merits, and a combination of these methods is used Surgery: The cancer must still be in the primary tumor stage A high degree of confidence that the entire tumor can be excised Removing the tumor without causing significant damage to vital organs Radiation therapy: is used to shrink or destroy tumors This approach requires that the tumor be localized X-ray radiation is used by focusing an X-ray beam on the tumor Immunologic Therapy: Utilize the immune system to eradicate the cancer This methodology attempts to boost the level of T-cell and B-cell The major role of T-cell is to destroy foreign cells, including malignant cells B-cell is produced in the bone marrow and lymph nodes, make antibodies in response to a foreign protein Section 2 Cancer Chemotherapy 一 Alkylating Agents （烷基化试剂） 1 Nitrogen mustards （氮芥） mechlorethamine Mechanism of Action 氮丙啶鎓 Alkylation of guanin