Deglycobleomycin A(6) analogues modified in the methylvalerate moiety

作者：Cai Xiaoqing; Zaleski Paul A; Cagir Ali; Hecht Sidney M^*

来源：Bioorganic & Medicinal Chemistry, 2011, 19(12): 3831-3844.

DOI：10.1016/j.bmc.2011.04.047

• Bleomycins
• Deglycobleomycin analogues
• Methylvalerate moiety
• DNA cleavage
• Solid-phase synthesis

Previous studies have indicated that the methylvalerate subunit of bleomycin (BLM) plays an important role in facilitating DNA cleavage by BLM and deglycoBLM. Eleven methylvalerate analogues have been synthesized and incorporated into deglycoBLM congeners by the use of solid-phase synthesis. The effect of the valerate moiety in the deglycoBLM analogues has been studied by comparison with the parent deglycoBLM A(5) using supercoiled DNA relaxation and sequence-selective DNA cleavage assays. All of the deglycoBLM analogues were found to effect the relaxation of the plasmid DNA. Those analogues having aromatic C4-substituents exhibited cleavage efficiency comparable to that of deglycoBLM A(5). Some, but not all, of the deglycoBLM analogues were also capable of mediating sequence-selective DNA cleavage.

• 出版日期2011-6-15