Discovery of TSAO derivatives with an unusual HIV-1 activity/resistance profile. 2006

Sonia de Castro, and Carlos García-Aparicio, and Kristel Van Laethem, and Federico Gago, and Esther Lobatón, and Erik De Clercq, and Jan Balzarini, and María-José Camarasa, and Sonsoles Velázquez
Instituto de Química Médica (C.S.I.C.), Juan de la Cierva 3, Madrid, Spain.

The very first TSAO derivative that lacks the 4''-amino group at the 3'-spiro moiety (compound 3) has been prepared and the effect of this modification on the activity/resistance profile has been evaluated. This molecule proved HIV-1 specific (NNRTI-characteristic). A mixture of wild-type and V106V/A or L234L/I mutations were found in the RT of some, but not all compound 3-resistant virus strains. Compound 3 does not select for the TSAO-specific E138K mutation in the RT. However, the compound markedly lost its antiviral potential against a variety of virus strains that contain NNRTI-characteristic mutations in RT including E138K. The deaminated TSAO compound must fit differently in the HIV-1 RT enzyme than its prototype TSAO-m(3)T.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013141 Spiro Compounds Cyclic compounds that include two rings which share a single atom (usually a carbon). The simplest example of this type of compound is Spiro[2.2]pentane, which looks like a bow tie. Compounds, Spiro
D013936 Thymidine A nucleoside in which THYMINE is linked to DEOXYRIBOSE. 2'-Deoxythymidine,Deoxythymidine,2' Deoxythymidine
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015498 HIV-2 An HIV species related to HIV-1 but carrying different antigenic components and with differing nucleic acid composition. It shares serologic reactivity and sequence homology with the simian Lentivirus SIMIAN IMMUNODEFICIENCY VIRUS and infects only T4-lymphocytes expressing the CD4 phenotypic marker. HTLV-IV,Human T-Lymphotropic Virus Type IV,Human immunodeficiency virus 2,LAV-2,HIV-II,Human Immunodeficiency Virus Type 2,Human T Lymphotropic Virus Type IV,Immunodeficiency Virus Type 2, Human,SBL-6669
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human

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