title: Binding thermodynamics of paromomycin, neomycin, neomycin-dinucleotide and -diPNA conjugates to bacterial and human rRNA.
abstract: Isothermal titration calorimetry (ITC) is a powerful technique able to evaluate the energetics of target-drug binding within the context of drug discovery. In this work, the interactions of RNAs reproducing bacterial and human ribosomal A-site, with two well-known antibiotic aminoglycosides, Paromomycin and Neomycin, as well as several Neomycin-dinucleotide and -diPNA conjugates, have been evaluated by ITC and the corresponding thermodynamic quantities determined. The comparison of the thermodynamic data of aminoglycosides and their chemical analogues allowed to select Neomycin-diPNA conjugates as the best candidates for antimicrobial activity.
authors.affiliation: Departament de Química Orgànica, Facultat de Química and Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Martí i Franquès, 1-11, 08028, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Alguacil
authors.affiliation: Departament de Química Orgànica, Facultat de Química and Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Martí i Franquès, 1-11, 08028, Barcelona, Spain.
authors.forename: Jordi
authors.identifier: http://orcid.org/0000-0002-8583-4930
authors.initials: J
authors.lastname: Robles
authors.affiliation: Departament de Química Analítica, Facultat de Química and Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Martí i Franquès, 1-11, 08028, Barcelona, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Ràfols
authors.affiliation: Departament de Química Analítica, Facultat de Química and Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Martí i Franquès, 1-11, 08028, Barcelona, Spain.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bosch
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002151:Calorimetry; D006801:Humans; D009355:Neomycin / Q000494:pharmacology; D010303:Paromomycin / Q000494:pharmacology; D011485:Protein Binding; D012329:RNA, Bacterial / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial; D012335:RNA, Ribosomal; D010303:Paromomycin; D009355:Neomycin
keywords: RNA; aminoglycosides; antibiotics; calorimetry; isothermal titration calorimetry (ITC); nucleic acids analogues