Bleomycin (BLM) is an antitumor antibiotic used clinically in combination chemotherapy in the treatment of head, neck and testicular cancer. We have solved the structure of cobalt-BLM green form, where the sixth ligand is an axial hydroperoxide.(J. Am. Chem. Soc. 118, 1268-1280 (1996)) We have set up a collaborative effort with Dale Boger's laboratory at Scripps.who has completed the total synthesis of BLM in a user friendly fashion. He has supplied us with a number of mutant-BLMs. All of these analogs have the two sugar moieties, gulose and mannose, removed. We have prepared the cobalt analog of deglyco-BLM and are determining its structure. This structure will serve as the prototype of all additional mutant structures. We have also recently solved the structure of cobalt-Blm brown form. In this case, the axial ligand is H20. Thus far we have been unable to define the screw sense of this analog. We have also acquired the data to solve the structure of phleomycin, an analog of BLM in which one of the thiazolium rings is reduced. Solutions of these structures is required for determination of their structures sequencing specifically to DNA.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000995-21
Application #
5221963
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
21
Fiscal Year
1996
Total Cost
Indirect Cost
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