Polynucleotide Recognition and Degradation by Bleomycin

Abstract

This chapter discusses the chemistry of nucleic acid degradation, deoxyribonucleic acid (DNA) sequence and structure recognition, and the mode of DNA and ribonucleic acid (RNA) interaction, with bleomycin. The finding that a natural product, bleomycin, can recognize specific DNA sequences and mediate the oxidative destruction of the deoxyribose moiety of DNA in a manner that ultimately leads to strand scission has made it the prototype for the design of simple molecular systems that function as “artificial nucleases.” The potential uses of such chemical nucleases range from tools in molecular biology research to the development of new chemotherapeutic agents. Like bleomycin, most of these systems rely on the redox nature of transition metals to promote nucleic acid oxidation. Bleomycin is used clinically, both as a single agent and in combination chemotherapy, for the treatment of several neoplasms, including squamous cell carcinomas, testicular tumors, and malignant lymphomas. It is used clinically as a mixture of structurally related molecules called “Blenoxane.” One intriguing aspect of the interaction of bleomycin, with double stranded DNA, is its selectivity for G-Y sequences. The minor groove of DNA in proximity to G-C sequences is believed to be shallower than the minor groove of A-T sequences, due to the 2-amino group of guanosine; moreover, some evidence suggests that the minor groove of G-C sequences is wider than that of A-T sequences.