This project involves the identification of Vinca alkaloid macromolecular interactions in cells and the characterization of the relationship of these associations to overall drug anti-neoplastic activity and drug-resistance mechancisms. Radioactive photactive analogues of vinblastine have been synthesized. The pharmacological activity of one of these analogues is compared to the parent drug. Macromolecular interactions are identified by photaffinity labeling and SDS-polyacrylamide gel electrophoresis. The labeled polypeptides are characterized and identified by immunoprecipitation. The mechanism of analogue binding to tubulin and inhibition of microtubule polymerization is being studied. New Vinca alkaloid binding proteins have been identified and their role in these processes is being examined. The relationship of drug-binding proteins to cellular drug-sensitivity and drug-resistance is being investigated.