Sequence-specific minor groove binding by bis-benzimidazoles: water molecules in ligand recognition
AUTOR(ES)
Bailly, Christian
FONTE
Oxford University Press
RESUMO
The binding of two symmetric bis-benzimidazole compounds, 2,2-bis-[4′-(3″-dimethylamino-1″-propyloxy)phenyl]-5,5-bi-1H-benzimidazole and its piperidinpropylphenyl analog, to the minor groove of DNA, have been studied by DNA footprinting, surface plasmon resonance (SPR) methods and molecular dynamics simulations in explicit solvent. The footprinting and SPR methods find that the former compound has enhanced affinity and selectivity for AT sequences in DNA. The molecular modeling studies have suggested that, due to the presence of the oxygen atom in each side chain of the former compound, a water molecule is immobilized and effectively bridges between side chain and DNA base edges via hydrogen bonding interactions. This additional contribution to ligand–DNA interactions would be expected to result in enhanced DNA affinity, as is observed.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=149830Documentos Relacionados
- Sequence-specific recognition and cleavage of DNA by metallobleomycin: minor groove binding and possible interaction mode.
- Binding of a hairpin polyamide in the minor groove of DNA: sequence-specific enthalpic discrimination.
- Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA.
- Sequence-specific arrest of primer extension on single-stranded DNA by an oligonucleotide-minor groove binder conjugate.
- Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin.
