Add time:07/20/2019         Source:sciencedirect.com

This paper describes chemical modification of the toxic agent Leucinostatin A and its conjugation with a monoclonal antibody. The molecule, isolated from a culture filtrate of Paecilomyces marquandii (Massee) Hughes, is a nonapeptide antibiotic with cytotoxic and phytotoxic properties. To evaluate its toxicity, and to improve its specificity as an antitumor agent, the molecule was conjugated to the monoclonal antibody AR-3, specific to human colorectal and ovarian carcinomas. The targeting ability of AR-3, bearing different amounts of toxic agent, was tested on related and unrelated cell lines. Stability of the ester linkage between Leucinostatin A and AR-3 was also studied.In this study we show that coupling of Leucinostatin A with a tumor-directed monoclonal antibody is a practical way to increase both the cytotoxicity and selectivity of the chemotherapeutic agent.

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