title: Rational design of pyrrolo.
abstract: Models have been developed for the interaction of the pyrrolo[1,2-a]benzimidazole (PBI) antitumor agents with the two-electron activating enzyme DT-diaphorase and the DNA major groove. The DT-diaphorase model and experimental results indicate that the S-enantiomer of 3-carbamido PBI can enantioselect ovarian cancers. The reduced PBI interacts with the DNA major groove at AT base pairs by forming Hoogsteen-like hydrogen bonds. The reduced 3-amino PBI forms three hydrogen bonds in the major groove with the amino group acting as an H-bond donor to the thymine carbonyl. The DNA-binding model will permit the design of major groove recognition agents.
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona, 85287-1604
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: A
authors.initials: A
authors.lastname: Suleman
authors.forename: E B
authors.initials: EB
authors.lastname: Skibo