Deglycobleomycin A6 analogues modified in the methylvalerate moiety

Xiaoqing Cai, Paul A. Zaleski, Ali Cagir, Sidney Hecht

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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 A5 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 A5. Some, but not all, of the deglycoBLM analogues were also capable of mediating sequence-selective DNA cleavage.

Original languageEnglish (US)
Pages (from-to)3831-3844
Number of pages14
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number12
DOIs
StatePublished - Jun 15 2011

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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