title: ESI-MS characterization of a novel pyrrole-inosine nucleoside that interacts with guanine bases.
abstract: Based on binding studies undertaken by electrospray ionization-mass spectrometry, a synthetic pyrrole-inosine nucleoside, 1, capable of forming an extended three-point Hoogsteen-type hydrogen-bonding interaction with guanine, is shown to form specific complexes with two different quadruplex DNA structures [dTG(4)T](4) and d(T(2)G(4))(4) as well as guanine-rich duplex DNA. The binding interactions of two other analogs were evaluated in order to unravel the structural features that contribute to specific DNA recognition. The importance of the Hoogsteen interactions was confirmed through the absence of specific binding when the pyrrole NH hydrogen-bonding site was blocked or removed. While 2, with a large blocking group, was not found to interact with virtually any form of DNA, 3, with the pyrrole functionality missing, was found to interact non-specifically with several types of DNA. The specific binding of 1 to guanine-rich DNA emphasizes the necessity of careful ligand design for specific sequence recognition.
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712-1167, United States.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Pierce
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Sherman
authors.forename: Janarthanan
authors.initials: J
authors.lastname: Jayawickramarajah
authors.forename: Candace M
authors.initials: CM
authors.lastname: Lawrence
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Sessler
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Brodbelt
mesh_terms: D001482:Base Composition; D001483:Base Sequence; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D007288:Inosine / Q000737:chemistry*; D008024:Ligands; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011758:Pyrroles / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013379:Substrate Specificity
chemical_list: D004277:DNA, Single-Stranded; D008024:Ligands; D009705:Nucleosides; D009841:Oligonucleotides; D011758:Pyrroles; D007288:Inosine; D006147:Guanine
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