DESIGN OF AN INSECTICIDAL ECDYSONE RECEPTOR ANTAGONIST

INCREASED AWARENESS OF THE HAZARDS THAT MANY SYNTHETIC INSECTICIDAL CHEMICALS POSE TO HUMAN AND ANIMAL HEALTH HAS CREATED AN URGENT NEED FOR ALTERNATIVE INSECTICIDES THAT TARGET PHYSIOLOGICAL SYSTEMS UNIQUE TO INSECT PESTS. DRIVEN BY CONCERN ABOUT THE TOXICITY OF SYNTHETIC INSECTICIDES (MANY ARE NEUROTOXINS), THEIR ENVIRONMENTAL INCOMPATIBILITY, AND THE PROFOUND TENDENCY OF INSECTS TO DEVELOP RESISTANCE TO INSECTICIDES, THE AGRICULTURAL INDUSTRY HAS BEGUN TO LOOK FAVORABLY AT EFFECTIVE BIOLOGICAL PEST-CONTROL METHODS THAT ARE BIODEGRADABLE AND PRODUCE FEWER TOXIC SIDE-EFFECTS. IN RESPONSE TO THE NEED FOR SAFER, ENVIRONMENTALLY-ACCEPTABLE INSECTICIDES, THE PROPOSED RESEARCH PROGRAM FOCUSES ON THE DEVELOPMENT OF NEW COMPOUNDS THAT WILL INTERFERE WITH INSECT METAMORPHOSIS AND DEVELOPMENT, BY BLOCKING THE ACTION OF THE STEROID MOLTING HORMONE 20-HYDROXYECDYSONE ("ECDYSONE"). ALTHOUGH THE USE OF ECDYSONE AS AN INSECTICIDE HAS BEEN CONSIDERED BEFORE, PROGRESS IN THIS AREA HAS BEEN HAMPERED BY THE STRUCTURAL COMPLEXITY AND SYNTHETIC INACCESSIBILITY OF THE NATIVE STEROID FOR LARGE-SCALE APPLICATION. WITH THIS IN MIND, IMMUNO PHARMACEUTICS, INC. PROPOSES TO APPLY THE TECHNOLOGY OF ANTIBODY-DIRECTED DRUG DESIGN TO THE DESIGN OF ECDYSONE ANTAGONISTS, A TECHNOLOGY WHICH DOES NOT REQUIRE PURIFICATION OF EITHER ECDYSONE OR ECDYSONE RECEPTORS.