Download or read book Studies Toward the Mechanism of Bleomycin written by Corin Deann Slown and published by ProQuest. This book was released on 2008 with total page 360 pages. Available in PDF, EPUB and Kindle. Book excerpt: The bleomycins are a class of glycopeptide antitumor antibiotics isolated by Umezawa and coworkers in 1966. Bleomycin A2 is the major component (70%) of the clinical anticancer drug Blenoxane, employed in the treatment of several forms of cancer. Through DNA binding and degradation, a process that is both metal ion and oxygen dependent, bleomycin A2 cleaves double stranded DNA selectively at 5'-GC or 5'-GT sites by minor groove C4'-H atom abstraction and subsequent fragmentation of the deoxyribose backbone. Many key questions concerning the mechanism and functional roles of the structural units still remain unanswered, including the nature of the metal-binding ligands and their arrangement in the metal complexes. Efforts to address these questions include the synthesis of 15N-labeled analogues of the pyrimidoblamic acid as well as the carbamoyl portion of the disaccharide, their incorporation into bleomycin A2 and subsequent Electron Nuclear Double Resonance (ENDOR) spectroscopy studies.