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.
