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Molecular Recognition of DNA by Hoechst Benzimidazoles: Exploring Beyond the Pyrrole‐Imidazole‐Hydroxypyrrole Polyamide‐Pairing Code
Author(s) -
Minehan Thomas G.,
Gottwald Konstanze,
Dervan Peter B.
Publication year - 2000
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(20000906)83:9<2197::aid-hlca2197>3.0.co;2-n
Subject(s) - chemistry , stereochemistry , footprinting , dna , minor groove , monomer , nuclease , imidazole , dodecameric protein , molecule , benzimidazole , biochemistry , base sequence , organic chemistry , polymer
A series of three‐ring analogs of the minor‐groove‐binding molecule Hoechst 33258 ( 1 ), consisting of benzimidazole (B), imidazopyridine (P), and hydroxybenzimidazole (H) monomers, have been synthesized in order to investigate both their sequence specificity and binding modes. MPE⋅Fe II Footprinting has revealed the preference of both PBB and BBB ligands for 5′‐WGWWW‐3′ and 5′‐WCWWW‐3′ tracts, as well as A⋅T‐rich sequences. Affinity‐cleavage titrations show no evidence for a 2 : 1 binding mode of these Hoechst analogs. Importantly, all derivatives are oriented in one direction at each of their binding sites. The implications of these results for the design of minor‐groove‐binding small molecules is discussed.