Design of Biofunctional Molecules based on Molecular Recognition

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The aim of this research project is to design a novel biofuctional molecule targeted to DNA,based on the elucidation of the DNA cleavage mechanisms of naturally occuring DNA-Cleaving molecules.1. Mechanistic Studies on the Action Mechanism of DNA-Cleaving Antitumor AntibioticsNatural antitumor antibiotics such as bleomycin, neocarzinostatin, kaprimycin, or duocarmycins are known to cleavage DNA at specific sites. We are able to elucidate the mechanisms of DNA cleavage induced by bleomycins, neocarzinostatin and kapurimycins by using oligonucleotides as a DNA substrate. We have also succeeded to design a unique oligomer probe which has a radical clock at the target site. By using this novel oligomer, we were able to demonstrate for the first time that C-4' radical of deoxyribose residues is actually generated by the action of activated bleomycins.2. Design of Sequence Specific DNA CleaversWe have succeeded to design several important sequence specefic DNA cleavers which could find wide spread application in molecular biology and photobiology. One of the notable DNA cleavers is the -GG- specific DNA-cleaving molecule upon photostimulation. We also designed a practically useful DNA-cleaving amino acid which can be incorporated into the desired sites of DNA-binding polypeptides.