title: The influence of the exocyclic amino group characteristic of GC base pairs on molecular recognition of specific nucleotide sequences in DNA by berenil and DAPI.
abstract: The expedient of preparing homologous DNA samples substituted with inosine for guanosine residues, 2,6-diaminopurine (DAP) for adenine residues, or both, has been used to investigate the role of the purine 2-amino group in determining the preferred binding sites for the drugs berenil [1,3-bis(4-phenylamidinium) triazene] and DAPI (4',6-diamidino-2-phenyl indole) on DNA. The selectivity of these two minor groove binders for AT-rich sequences is seen to be radically altered in the substituted DNA molecules. Neither berenil nor DAPI bind to DAP-substituted DNA where all purine residues bear a 2-amino group. By contrast, they bind to AT-rich, IC-rich and even mixed sequences of the inosine DNA where all purine residues lack the 2-amino group. With the inosine and DAP double substituted DNA, both berenil and DAPI bind preferentially to IC-rich clusters instead of their canonical tracts endowed with an extra 2-amino group through substitution with DAP. These results establish that the location of the purine 2-amino group represents a critical determinant for recognition of DNA nucleotide sequences by the two drugs.
authors.affiliation: Department of Pharmacology, University of Cambridge, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Waring
authors.forename: C
authors.initials: C
authors.lastname: Bailly
mesh_terms: D015075:2-Aminopurine / Q000031:analogs & derivatives / Q000378:metabolism; D000225:Adenine / Q000378:metabolism; D000588:Amines / Q000378:metabolism; D001482:Base Composition; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D018983:DNA Footprinting; D003850:Deoxyribonuclease I / Q000378:metabolism; D004133:Diminazene / Q000031:analogs & derivatives* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005456:Fluorescent Dyes / Q000378:metabolism; D006151:Guanosine / Q000378:metabolism; D006860:Hydrogen Bonding; D007211:Indoles / Q000378:metabolism*; D007288:Inosine / Q000378:metabolism; D007364:Intercalating Agents / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010957:Plasmids / Q000235:genetics
chemical_list: D000588:Amines; D005456:Fluorescent Dyes; D007211:Indoles; D007364:Intercalating Agents; D006151:Guanosine; D015075:2-Aminopurine; C007293:DAPI; C007300:2,6-diaminopurine; D007288:Inosine; D004247:DNA; D003850:Deoxyribonuclease I; D000225:Adenine; C003915:diminazene aceturate; D004133:Diminazene