Dependence of DNA sequence selectivity and cell cytotoxicity on azinomycin A and B epoxyamide stereochemistry.
Evaluation of the importance of C18/C19 stereochemistry of azinomycin A/B epoxyamide partial structures with respect to DNA alkylation sequence selectivity is reported using a unique assay with a DNA oligomer containing imbedded normal (5'-GGC-3'/3'-CCG-5') and inverted (5'-CGG-3'/3'-GCC-5') azinomycin consensus cross-linking sequences. Both species were found to have unique selectivity profiles and alkylate DNA in a manner distinct from azinomycin B. Computational docking experiments support altered binding modes for the enantiomers.
Coleman
Robert S
RS
Department of Chemistry, The Ohio State University, Columbus, OH 43210, USA. coleman@chemistry.ohio-state.edu
Woodward
Robert L
RL
Hayes
Amy M
AM
Crane
Erika A
EA
Artese
Anna
A
Ortuso
Francesco
F
Alcaro
Stefano
S
D000478:Alkylation; D053961:Azabicyclo Compounds; D001483:Base Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry*; D004151:Dipeptides; D004852:Epoxy Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D006020:Glycopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D006147:Guanine / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D036341:Intercellular Signaling Peptides and Proteins; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D009690:Nucleic Acid Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D013237:Stereoisomerism
D053961:Azabicyclo Compounds; D004151:Dipeptides; D004852:Epoxy Compounds; D006020:Glycopeptides; D036341:Intercellular Signaling Peptides and Proteins; D009281:Naphthalenes; D010455:Peptides; C515726:azinomycin epoxide; C051055:azinomycin B; C051054:azinomycin A; D006147:Guanine; D004247:DNA