title: Structure-activity relationship studies on a Trp dendrimer with dual activities against HIV and enterovirus A71. Modifications on the amino acid.
abstract: We have recently described a new class of dendrimers with tryptophan (Trp) on the surface that show dual antiviral activities against HIV and EV71 enterovirus. The prototype compound of this family is a pentaerythritol derivative with 12 Trps on the periphery. Here we complete the structure-activity relationship studies of this family to identify key features that might be significant for the antiviral activity. With this aim, novel dendrimers containing different amino acids (aromatic and non-aromatic), tryptamine (a "decarboxylated" analogue of Trp) and N-methyl Trp on the periphery have been prepared. Dendrimer with N-Methyl Trp was the most active against HIV-1 and HIV-2 while dendrimer with tyrosine was endowed with the most potent antiviral activity against EV71. This tyrosine dendrimer proved to inhibit a large panel of EV71 clinical isolates (belonging to different clusters) in the low nanomolar/high picomolar range. In addition, a new synthetic procedure (convergent approach) has been developed for the synthesis of the prototype and some other dendrimers. This convergent approach proved more efficient (higher yields, easier purification) than the divergent approach previously reported.
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Martínez-Gualda
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000, Leuven, Belgium.
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Rivero-Buceta
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Madrid, Spain.
authors.forename: Aida
authors.initials: A
authors.lastname: Flores
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Madrid, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Quesada
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000, Leuven, Belgium.
authors.forename: Sam
authors.initials: S
authors.lastname: Noppen
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000, Leuven, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Liekens
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000, Leuven, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Schols
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000, Leuven, Belgium.
authors.forename: Carmen
authors.initials: C
authors.lastname: Mirabelli
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Madrid, Spain.
authors.forename: María-José
authors.initials: MJ
authors.lastname: Camarasa
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Madrid, Spain. Electronic address: anarosa@iqm.csic.es.
authors.forename: Ana
authors.initials: A
authors.lastname: San-Félix
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D050091:Dendrimers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D029821:Enterovirus A, Human / Q000187:drug effects*; D004769:Enterovirus Infections / Q000821:virology; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects*; D006801:Humans; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000596:Amino Acids; D019380:Anti-HIV Agents; D000998:Antiviral Agents; D050091:Dendrimers; C028129:tryptophan methyl ester; D014364:Tryptophan
keywords: AIDS; Antiviral agents; EV71; HFMD; HIV; Tryptophan