TENTH INTERNATIONAL SYMPOSIUM ON PTERIDINES

这项赠款提案的目的是申请资金用于部分 支持第十届国际化学和环境科学研讨会 与化疗有关的蝶呤类药物的生物学。研讨会将是 1993年3月在阿拉巴马州佩尔迪多海滩举行。叶酸，抗叶酸 而生物蝶呤的衍生物是研究最广泛的 蝶形目。叶酸拮抗剂，如甲氨蝶呤和甲氧苄啶 广泛用于治疗，前者用于癌症，后者用于治疗 传染病。在过去的十年里，几种基于叶酸的酶 被确定为抗肿瘤广告的潜在目标 抗菌化疗和这些酶的新型抑制剂是 正在开发中。这些酶是琼脂甲酰转移酶， 叶基多谷氨酸合成酶和AICAR甲酰基转移酶。此外, 关于多谷氨酰化作为一种主要的 抗叶酸细胞毒性的决定因素正在几个方面进行研究 实验室。这些调查正在开辟新的途径和 癌症和微生物感染的化疗机会。 Biopterin是某些酶促羟化的重要辅因子 反应。生物蝶呤代谢异常被归因于 几种疾病，包括苯丙酮尿症。有相当多的 目前人们对了解抗病毒作用的机制感兴趣 抗叶酸的炎症特性。拟议的研讨会将 由个人研究报告组成，关于发生，化学， 蝶呤类药物的代谢、功能和化疗方面。这个 研讨会的目的是让蝶啶化学家齐聚一堂， 来自美国和其他国家的生物化学家和化学治疗师 各国在创造性的氛围中互动，并记录当前 研讨会卷中的进展。

The purpose of this grant proposal is to request funds for partial support for the 10th International Symposium on the Chemistry and Biology of Pteridines in relation to chemotherapy. The symposium will be held at Perdido Beach, Alabama in March of 1993. Folic acid, Antifolates and Biopterin derivatives are the most extensively investigates Pteridines. Folate antagonists such as Methotrexate and Trimethoprim are widely used therapeutically, the former for cancer, and the latter for infectious diseases. During the last decade several folate-based enzymes were identified to be potential targets for antineoplastic ad antimicrobial chemotherapy and novel inhibitors of these enzymes are being developed. The enzymes are GAR formyltransferase, folylpolyglutamate synthetase, and AICAR formyltransferase. In addition, investigations regarding the role of polyglutamaylation as a major determinant of antifolate cytotoxicity are being pursued in several laboratories. These investigations are opening new avenues and opportunities for the chemotherapy of cancer and microbial infections. Biopterin is an essential cofactor for certain enzymatic hydroxylation reactions. Abnormalities of biopterin metabolism have been attributed to several diseases, that include phenylketonuria. There is considerable current interest in understanding the mechanisms of the anti- inflammatory properties of antifolates. The proposed symposium will consist of individual research reports on the occurrence, chemistry, metabolism, function and chemotherapeutic aspects of pteridines. The objective of the symposium is to bring together pteridine chemists, biochemists and chemotherapists from the United States and other countries to interact in a creative atmosphere and to document current advances in a symposium volume.