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VITAMIN B-12 ANALOGS VIA TRANSITION METAL POLYMERS

$37,516F32FY2000CANIH

University Of California Berkeley, Berkeley CA

Investigators

Abstract

DESCRIPTION The design of unique vitamin B-12 analogs for DNA recognition and cleavage by transition metal polymer chemistry is described. Cobalt(III) analogs that are specifically designed to be easily modified for binding the metal cobalt with a cyclic polymer. Standard reduction of the metal center followed by addition of an alkyl halide will be used to attach the alkyl reagent. A binding and trans-activating group is next attached to the metal-cyclic polymer system that is designed to recognize and bind to specific DNA sites and activate the release of the therapeutic unit alkyl group attached to the cobalt metal center. Introduction of this system into DNA is followed by photolysis and is expected to cleave DNA. The DNA cleavage and site specificity are to be observed by typical assay techniques and Nuclear Magnetic Resonance Spectroscopy (NMR).

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