title: Sequence specific recognition of DNA by tailor-made hairpin conjugates of achiral seco-cyclopropaneindoline-2-benzofurancarboxamide and pyrrole-imidazole polyamides.
abstract: Hairpin conjugates of achiral seco-cyclopropaneindoline-2-benzofurancarboxamide (achiral seco-CI-Bf) and three diamides (ImPy 1, PyIm 2, and PyPy 3, where Py is pyrrole, and Im is imidazole), linked by a gamma-aminobutyrate group, were synthesized. The sequence-specific covalent alkylation of the achiral CI moiety with adenine-N3 in the minor groove was ascertained by thermally induced DNA cleavage experiments. The results provide evidence that hairpin conjugates of achiral seco-CI-Bf-gamma-polyamides could be tailored to target specific DNA sequences according to a set of general rules: the achiral CI moiety selectively reacts with adenine-N3, a stacked pair of imidazole/benzofuran prefers a G/C base pair, and a pyrrole/benzofuran prefers an A/T or T/A base pair. Models for the binding of hairpin conjugates 1-3 with sequences 5'-TCA(888)G-3', 5'-CAA(857)C-3', and 5'-TTA(843)C-3' are proposed.
authors.affiliation: Department of Chemistry, Furman University, Greenville, SC 29613, United States.
authors.forename: Carly A
authors.initials: CA
authors.lastname: Price
authors.forename: Brian M
authors.initials: BM
authors.lastname: Lingerfelt
authors.forename: Heather L
authors.initials: HL
authors.lastname: Handl
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kiakos
authors.forename: John A
authors.initials: JA
authors.lastname: Hartley
authors.forename: Moses
authors.initials: M
authors.lastname: Lee
mesh_terms: D020856:AT Rich Sequence / Q000502:physiology; D000577:Amides / Q000737:chemistry / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D001572:Benzofurans / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D004247:DNA / Q000235:genetics* / Q000378:metabolism* / Q000528:radiation effects; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020862:GC Rich Sequence / Q000502:physiology; D006358:Hot Temperature; D007093:Imidazoles / Q000737:chemistry*; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011758:Pyrroles / Q000737:chemistry*; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D000577:Amides; D000951:Antigens, Neoplasm; D001572:Benzofurans; D004268:DNA-Binding Proteins; D007093:Imidazoles; D011758:Pyrroles; D004247:DNA; D004250:DNA Topoisomerases, Type II