The bleomycins are a family of glycopeptides derived antitumor antibiotics originally isolated from Streptomyces verticillus. Some of the bleomycins are used clinically for the treatment of squamous cell carcinomas and malignant lymphomas. While numerous studies of bleomycin have been carried out in the past few decades, few of these have addressed two remarkable properties of bleomycin, namely its tumor seeking properties and the way in which it targets its DNA substrates under physiological conditions. The present project is based on new strategies which provide (i) a facile method for monitoring the tumor seeking properties of bleomycin and (ii) an approach for identifying high affinity nucleic acid targets for bleomycin. Goals of the project include identification of the structural elements in bleomycin that are required for tumor targeting, as well as the cellular constituents that are recognized. Also proposed is the identification of DNA motifs that are bound and cleaved with exceptionally high efficiency by bleomycin.
The bleomycins are used clinically for the treatment of certain tumors that occur in soft tissues. The studies proposed here will facilitate an understanding of the way that this drug targets tumors, and binds to and degrades the nucleic acids in tumor tissue. As such, these studies will enable the preparation of bleomycins with improved properties.
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