title: Assessment of new triplet forming artificial nucleobases as RNA ligands directed towards HCV IRES IIId loop.
abstract: We report the synthesis of two new artificial nucleobase scaffolds, 1 and 2, featuring adequate hydrogen bonding donors and acceptors for the molecular recognition of U:A and C:G base pairs, respectively. The tethering of these structures to various amino acids and the assessment of these artificial nucleobase-amino acid conjugates as RNA ligands against a model of HCV IRES IIId domain are also reported. Compound 1e displayed the highest affinity (Kdtwice lower than neomycin - control). Moreover, it appears that this interaction is enthalpically and entropically favored.
authors.affiliation: Université Côte d'Azur, CNRS, Institut de Chimie de Nice UMR7272, 06108 Nice, France; CAPES Foundation, Ministry of Education of Brazil, Brasília DF 70040-020, Brazil.
authors.forename: Mauro
authors.initials: M
authors.lastname: Safir Filho
authors.affiliation: Université Côte d'Azur, CNRS, Institut de Chimie de Nice UMR7272, 06108 Nice, France.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Martin
authors.affiliation: Université Côte d'Azur, CNRS, Institut de Chimie de Nice UMR7272, 06108 Nice, France. Electronic address: benhida@unice.fr.
authors.forename: Rachid
authors.initials: R
authors.lastname: Benhida
mesh_terms: D020121:5' Untranslated Regions / Q000187:drug effects*; D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D020029:Base Pairing / Q000187:drug effects; D001483:Base Sequence; D016174:Hepacivirus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology; D006801:Humans; D008024:Ligands; D009690:Nucleic Acid Conformation; D011687:Purines / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020121:5' Untranslated Regions; D000596:Amino Acids; D000998:Antiviral Agents; D008024:Ligands; D011687:Purines; D011743:Pyrimidines; D012367:RNA, Viral
keywords: Binding assay; Hepatitis virus C; IRES IIId loop; Inhibitors; RNA ligands