Molecular recognition between ligands and nucleic acids: Novel pyridine- and benzoxazole-containing agents related to Hoechst 33258 that exhibit altered DNA sequence specificity deduced from footprinting analysis and spectroscopic studies

Journal Article · · Chemical Research in Toxicology; (USA)

DOI:https://doi.org/10.1021/tx00015a013· OSTI ID:6415406

Bathini, Y; Rao, K E; Shea, R G; Lown, J W ^[1]

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1. Univ. of Alberta, Edmonton (Canada)

The syntheses of certain analogues of the DNA minor groove binding agent Hoechst 33258 designed to exhibit altered sequence recognition are described. The structural modifications include the following: substitution of pyridine for the benzene ring of the benzimidazole moiety, replacement of one benzimidazole unit by a benzoxazole in the two possible orientations with respect to the DNA receptor, and a synthesis of 2,2{prime}-m-phenylenebis(6-(4-methyl-1-piperazinyl)benzimidazole). Sequence recognition of these agents on a HindIII/EcoRI fragment of pBR322 DNA was determined by MPE footprinting procedures. Some of the analogues exhibited altered DNA sequence preference compared with Hoechst 33258. In particular, a structure bearing a benzoxazole moiety with the oxygen oriented inward to the minor groove together with an inward-directed pyridine nitrogen appears to confer the property of recognition of a GC base pair within the binding sequence. The possible factors, structural, stereochemical, and electrostatic, contributing to the altered DNA sequence recognition properties are discussed.

• OSTI ID: 6415406
• Journal Information: Chemical Research in Toxicology; (USA), Journal Name: Chemical Research in Toxicology; (USA) Vol. 3:3; ISSN 0893-228X; ISSN CRTOE
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
560300 -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AZINES
BONDING
DNA
FABRICATION
HETEROCYCLIC COMPOUNDS
JOINING
LIGANDS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRIDINE
PYRIDINES
SPECTROSCOPY
STRUCTURAL CHEMICAL ANALYSIS