title: Recognition of the DNA minor groove by thiazotropsin analogues.
abstract: Solution-phase self-association characteristics and DNA molecular-recognition properties are reported for three close analogues of minor-groove-binding ligands from the thiazotropsin class of lexitropsin molecules; they incorporate isopropyl thiazole as a lipophilic building block. Thiazotropsin B (AcImPy(iPr) ThDp) shows similar self-assembly characteristics to thiazotropsin A (FoPyPy(iPr) ThDp), although it is engineered, by incorporation of imidazole in place of N-methyl pyrrole, to swap its DNA recognition target from 5'-ACTAGT-3' to 5'-ACGCGT-3'. Replacement of the formamide head group in thiazotropsin A by nicotinamide in AIK-18/51 results in a measureable difference in solution-phase self-assembly character and substantially enhanced DNA association characteristics. The structures and associated thermodynamic parameters of self-assembled ligand aggregates and their complexes with their respective DNA targets are considered in the context of cluster targeting of DNA by minor-groove complexes.
authors.affiliation: Department of Pharmacy, An-Najah National University, University Street, Nablus (Palestine); Present address: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 2J7 (Canada).
authors.forename: Hasan Y
authors.initials: HY
authors.lastname: Alniss
authors.forename: Marie-Virginie
authors.initials: MV
authors.lastname: Salvia
authors.forename: Mykhailo
authors.initials: M
authors.lastname: Sadikov
authors.forename: Igor
authors.initials: I
authors.lastname: Golovchenko
authors.forename: Nahoum G
authors.initials: NG
authors.lastname: Anthony
authors.forename: Abedawn I
authors.initials: AI
authors.lastname: Khalaf
authors.forename: Simon P
authors.initials: SP
authors.lastname: MacKay
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Suckling
authors.forename: John A
authors.initials: JA
authors.lastname: Parkinson
mesh_terms: D002151:Calorimetry; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D008024:Ligands; D013844:Thiazoles; C488075:thiazotropsin A; C512183:thiazotropsin B; D004247:DNA
keywords: DNA recognition; NMR spectroscopy; isothermal titration calorimetry; minor-groove binders; self-assembly; thiazotropsins