title: Synthesis of {[5-(adenin-9-yl)-2-furyl]methoxy}methyl phosphonic acid and evaluations against human adenylate kinases.
abstract: AMP mimics constitute an important class of therapeutic derivatives to treat diseases where the pool of ATP is involved. A new phosphonate derivative of 9-(5-hydroxymethylfuran-2-yl)adenine was synthesized in a multi-step sequence from commercially available adenosine. Its ability to behave as a substrate of human adenylate kinases 1 and 2 was assessed. The phosphonate was shown to be a moderate but selective substrate of the mitochondrial human AK2, better than well-known antiviral acyclic phosphonates 9-(2-phosphonomethoxyethyl)adenine (PMEA, Adefovir) and (R)-9-(2-phosphonomethoxypropyl)adenine (PMPA, Tenofovir). Putative binding mode within adenylate kinase NMP site revealed by molecular docking in comparison to AMP native substrate allowed to illustrate this selective behavior.
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-UM 1-UM 2, cc 1705, Université Montpellier 2, Place Eugène Bataillon, 34095 Montpellier cedex 5, France.
authors.forename: Malika
authors.initials: M
authors.lastname: Kaci
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-UM 1-UM 2, cc 1705, Université Montpellier 2, Place Eugène Bataillon, 34095 Montpellier cedex 5, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Uttaro
authors.affiliation: Enzymologie Moléculaire et Fonctionnelle, UMR 8256 UPMC-CNRS, ERL INSERM U1164, Université Pierre et Marie Curie, 7 Quai St-Bernard, 75252 Paris cedex 5, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Lefort
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-UM 1-UM 2, cc 1705, Université Montpellier 2, Place Eugène Bataillon, 34095 Montpellier cedex 5, France. Electronic address: christophe.mathe@univ-montp2.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Mathé
authors.affiliation: Enzymologie Moléculaire et Fonctionnelle, UMR 8256 UPMC-CNRS, ERL INSERM U1164, Université Pierre et Marie Curie, 7 Quai St-Bernard, 75252 Paris cedex 5, France.
authors.forename: Chahrazade
authors.initials: C
authors.lastname: El Amri
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-UM 1-UM 2, cc 1705, Université Montpellier 2, Place Eugène Bataillon, 34095 Montpellier cedex 5, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Périgaud
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000263:Adenylate Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000595931:((5-(adenin-9-yl)-2-furyl)methoxy)methyl phosphonic acid; D063065:Organophosphonates; D000263:Adenylate Kinase; C110939:adenylate kinase 1; C110938:adenylate kinase 2; D000225:Adenine
keywords: Adenosine; Analogue/AMP mimics; Kinase; Nucleoside; Phosphonate; Phosphotransfer