The cellular targets of novel enediynes based on antitumor agents will be identified. To achieve this goal a small library of bifunctional enediynes will be chemically synthesized. These agents are designed to immobilize specific cellular targets, including DNA and proteins. Customized bioassay methods will be employed to delineate the required functionality to achieve in vitro biological activity against various tumor types. In tandem with this study, chemical interception of the diyl radicals derived from Bergman cycloaromatization will be investigated using a variety of atom transfer agents. It is expected that this will result in the chemical synthesis of numerous analogs of the cycloaromatized product which may have medicinal value in their own right. The study will throw new light on the mode of action of the enediynes and is expected to lead to the development of new antitumor agents and affinity cleavage systems.

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National Institute of General Medical Sciences (NIGMS)
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Medicinal Chemistry Study Section (MCHA)
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Northeastern University
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