title: AzaHx, a novel fluorescent, DNA minor groove and G·C recognition element: Synthesis and DNA binding properties of a p-anisyl-4-aza-benzimidazole-pyrrole-imidazole (azaHx-PI) polyamide.
abstract: The design, synthesis, and DNA binding properties of azaHx-PI or p-anisyl-4-aza-benzimidazole-pyrrole-imidazole (5) are described. AzaHx, 2-(p-anisyl)-4-aza-benzimidazole-5-carboxamide, is a novel, fluorescent DNA recognition element, derived from Hoechst 33258 to recognize G·C base pairs. Supported by theoretical data, the results from DNase I footprinting, CD, ΔT(M), and SPR studies provided evidence that an azaHx/IP pairing, formed from antiparallel stacking of two azaHx-PI molecules in a side-by-side manner in the minor groove, selectively recognized a C-G doublet. AzaHx-PI was found to target 5'-ACGCGT-3', the Mlu1 Cell Cycle Box (MCB) promoter sequence with specificity and significant affinity (K(eq) 4.0±0.2×10(7) M(-1)).
authors.affiliation: Department of Chemistry, Hope College, Holland, MI 49423, United States.
authors.forename: Vijay
authors.initials: V
authors.lastname: Satam
authors.affiliation: Department of Chemistry, Hope College, Holland, MI 49423, United States.
authors.forename: Balaji
authors.initials: B
authors.lastname: Babu
authors.affiliation: Department of Chemistry, Hope College, Holland, MI 49423, United States.
authors.forename: Pravin
authors.initials: P
authors.lastname: Patil
authors.affiliation: Department of Chemistry, Hope College, Holland, MI 49423, United States.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Brien
authors.affiliation: Department of Chemistry, Hope College, Holland, MI 49423, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Olson
authors.affiliation: Department of Chemistry, Hope College, Holland, MI 49423, United States.
authors.forename: Mia
authors.initials: M
authors.lastname: Savagian
authors.affiliation: Department of Chemistry, Hope College, Holland, MI 49423, United States.
authors.forename: Megan
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Hope College, Holland, MI 49423, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mepham
authors.affiliation: Department of Chemistry, Erskine College, Due West, SC 29639, United States.
authors.forename: Laura Beth
authors.initials: LB
authors.lastname: Jobe
authors.affiliation: Cancer Research UK Drug-DNA Interactions Research Group, UCL Cancer Institute, London WC1E 6BT, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Bingham
authors.affiliation: Cancer Research UK Drug-DNA Interactions Research Group, UCL Cancer Institute, London WC1E 6BT, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: Pett
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Chemistry, John Carroll University, University Heights, OH 44118, United States.
authors.forename: Maddi
authors.initials: M
authors.lastname: Ferrara
authors.affiliation: Department of Chemistry, John Carroll University, University Heights, OH 44118, United States.
authors.forename: Chrystal D
authors.initials: CD
authors.lastname: Bruce
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States.
authors.forename: W David
authors.initials: WD
authors.lastname: Wilson
authors.affiliation: Department of Chemistry, Hope College, Holland, MI 49423, United States; Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States. Electronic address: mosesleenf@gmail.com.
authors.forename: Moses
authors.initials: M
authors.lastname: Lee
authors.affiliation: Cancer Research UK Drug-DNA Interactions Research Group, UCL Cancer Institute, London WC1E 6BT, UK.
authors.forename: John A
authors.initials: JA
authors.lastname: Hartley
authors.affiliation: Cancer Research UK Drug-DNA Interactions Research Group, UCL Cancer Institute, London WC1E 6BT, UK.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kiakos
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D020029:Base Pairing; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D060326:Chemistry Techniques, Synthetic; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000737:chemistry; D015195:Drug Design; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry*; D011401:Promoter Regions, Genetic; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D001562:Benzimidazoles; D004268:DNA-Binding Proteins; D005456:Fluorescent Dyes; D009757:Nylons; D011758:Pyrroles; C000607677:p-anisyl-4-aza-benzimidazole-pyrrole-imidazole; D004247:DNA; D003850:Deoxyribonuclease I; D004250:DNA Topoisomerases, Type II
keywords: AzaHx; DNA; Distamycin; Hoechst 33258; Hx-amides; Minor groove; Polyamides; Sequence recognition