TENTH INTERNATIONAL SYMPOSIUM ON PTERIDINES

本赠款提案的目的是申请部分资金， 支持第十届国际化学研讨会， 与化疗相关的蝶啶类生物学。研讨会将在 1993年3月在亚拉巴马Perdido海滩举行。叶酸，抗叶酸剂 生物蝶呤衍生物是研究最广泛的 蝶啶叶酸拮抗剂如甲氨蝶呤和甲氧苄氨嘧啶， 广泛用于治疗，前者用于癌症，后者用于 传染病在过去的十年中，几种基于叶酸的酶 被确定为抗肿瘤AD的潜在靶点 抗微生物化学疗法和这些酶的新型抑制剂， 正在开发中。这些酶是GAR甲酰转移酶， 叶酰聚谷氨酸合成酶和AICAR甲酰基转移酶。此外，本发明还提供了一种方法， 关于多聚谷氨酰化作为一种主要的 抗叶酸剂细胞毒性决定因素正在几个研究中进行 laboratories.这些调查正在开辟新的途径， 为癌症和微生物感染的化疗提供机会。 生物蝶呤是某些酶促羟化反应的必需辅因子 反应.生物蝶呤代谢的异常归因于 包括苯丙酮尿症在内的几种疾病。有相当大 目前对了解抗- 抗叶酸剂的炎症特性。拟议的研讨会将 包括个别研究报告的发生，化学， 蝶啶类化合物的代谢、功能和化学治疗方面。的 研讨会的目的是汇集蝶啶化学家， 来自美国和其他国家的生物化学家和化学治疗师 各国在创造性的气氛中进行互动， 专题讨论会卷中的进展。

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.