ArticleBioorganic & medicinal chemistry2016
Zorbamycin has a different DNA sequence selectivity compared with bleomycin and analogues.
Article in Bioorganic & medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 8 citations in OpenAlex.
- The Interaction of the Metallo-Glycopeptide Anti-Tumour Drug Bleomycin with DNA.International journal of molecular sciences · 2018Review
- Metal-mediated diradical tuning for DNA replication arrest via template strand scission.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The DNA sequence specificity of bleomycin cleavage in a systematically altered DNA sequence.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Bleomycin (BLM) is used clinically in combination with a number of other agents for the treatment of several types of tumours. Members of the BLM family of drugs include zorbamycin (ZBM), phleomycin D1, BLM A2 and BLM B2. By manipulating the BLM biosynthetic machinery, we have produced two new BLM analogues, BLM Z and 6'-deoxy-BLM Z, with the latter exhibiting significantly improved DNA cleavage activity. Here we determined the DNA sequence specificity of BLM Z, 6'-deoxy-BLM Z and ZBM, in comparison with BLM, with high precision using purified plasmid DNA and our recently developed technique. It was found that ZBM had a different DNA sequence specificity compared with BLM and the BLM analogues. While BLM and the BLM analogues showed a similar DNA sequence specificity, with TGTA sequences as the main site of cleavage, ZBM exhibited a distinct DNA sequence specificity, with both TGTA and TGTG as the predominant cleavage sites. These differences in DNA sequence specificity are discussed in relation to the structures of ZBM, BLM and the BLM analogues. Our findings support the strategy of manipulating the BLM biosynthetic machinery for the production of novel BLM analogues, difficult to prepare by total synthesis; some of which could have beneficial cancer chemotherapeutic properties.
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Registered trials
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