Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Alkylation
-
Azabicyclo Compounds
-
Base Sequence
-
Cell Line, Tumor
-
Cell Survival / drug effects
-
DNA / chemistry*
-
Dipeptides
-
Epoxy Compounds / chemical synthesis*
-
Epoxy Compounds / chemistry
-
Epoxy Compounds / toxicity*
-
Glycopeptides / chemical synthesis
-
Glycopeptides / chemistry*
-
Glycopeptides / toxicity*
-
Guanine / chemistry
-
Humans
-
Hydrogen Bonding
-
Intercellular Signaling Peptides and Proteins
-
Naphthalenes / chemical synthesis*
-
Naphthalenes / chemistry
-
Naphthalenes / toxicity*
-
Nucleic Acid Conformation
-
Peptides / chemical synthesis
-
Peptides / chemistry*
-
Peptides / toxicity*
-
Stereoisomerism
Substances
-
Azabicyclo Compounds
-
Dipeptides
-
Epoxy Compounds
-
Glycopeptides
-
Intercellular Signaling Peptides and Proteins
-
Naphthalenes
-
Peptides
-
azinomycin epoxide
-
azinomycin B
-
azinomycin A
-
Guanine
-
DNA