title: Anti-HIV-1 activity of a tripodal receptor that recognizes mannose oligomers.
abstract: The glycoprotein gp120 of the HIV-1 viral envelope has a high content in mannose residues, particularly α-1,2-mannose oligomers. Compounds that interact with these high-mannose type glycans may disturb the interaction between gp120 and its (co)receptors and are considered potential anti-HIV agents. Previously, we demonstrated that a tripodal receptor (1), with a central scaffold of 1,3,5-triethylbenzene substituted with three 2,3,4-trihydroxybenzoyl groups, selectively recognizes α-1,2-mannose polysaccharides. Here we present additional studies to determine the anti-HIV-1 activity and the mechanism of antiviral activity of this compound. Our studies indicate that 1 shows anti-HIV-1 activity in the low micromolar range and has pronounced gp120 binding and HIV-1 integrase inhibitory capacity. However, gp120 binding rather than integrase inhibition seems to be the primary mechanism of antiviral activity of 1.
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Rivero-Buceta
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain; ABG Patentes, Avenida de Burgos 16D, 28036 Madrid, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Carrero
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain; Euroquímica S.A., Crta. Yeles, Km 2, Illescas, Toledo, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Casanova
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain; Centro de Química Orgánica "Lora-Tamayo" (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Elisa G
authors.initials: EG
authors.lastname: Doyagüez
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Madrona
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Quesada
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Peréz-Pérez
authors.affiliation: Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN-CSIC), Jose Antonio Novais 10, 28040 Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Mateos
authors.affiliation: Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN-CSIC), Jose Antonio Novais 10, 28040 Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Bravo
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Mathys
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Sam
authors.initials: S
authors.lastname: Noppen
authors.affiliation: Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Kiselev
authors.affiliation: Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Christophe
authors.initials: C
authors.lastname: Marchand
authors.affiliation: Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Liekens
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Camarasa
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain. Electronic address: anarosa@iqm.csic.es.
authors.forename: Ana
authors.initials: A
authors.lastname: San-Félix
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015699:HIV Envelope Protein gp120 / Q000037:antagonists & inhibitors*; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D008351:Mannans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D019428:HIV Integrase Inhibitors; D008351:Mannans; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1
keywords: AIDS; Antiviral agents; HIV; Integrase; Polyphenols