BIOMAT Database Logo BIOMAT Database Logo

4'-Acylated thymidine 5'-triphosphates: a tool to increase selectivity towards HIV-1 reverse transcriptase. 1998

A Marx, and M Amacker, and M Stucki, and U Hübscher, and T A Bickle, and B Giese
Department of Chemistry, University of Basel, St Johanns-Ring 19, CH-4056 Basel, Switzerland.

4'-Acylated thymidines represent a new class of DNA chain terminators, since they have been shown to act as post-incorporation chain-terminating nucleotides despite the presence of a free 3'-hydroxyl group. Here, we describe the action of the 4'-acetyl- (MeTTP) and 4'-propanoylthymidine 5'-triphosphate (EtTTP) on HIV-1 reverse transcriptase in RNA- and DNA-dependent DNA synthesis and on DNA synthesis catalyzed by the cellular DNA polymerases alpha, beta, delta and epsilon. MeTTP exhibits a high selectivity towards HIV-1 reverse transcriptase. By the use of the bulkier propanoyl group as the 4'-substituent of the nucleoside 5'-triphosphate, selectivity towards HIV-1 reverse transcriptase could be increased without affecting substrate efficiency. Thus, 4'-modifications may serve as a tool to increase selectivity towards HIV-1 reverse transcriptase.

UI MeSH Term Description Entries
D009838 Oligodeoxyribonucleotides A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties. Oligodeoxynucleotide,Oligodeoxyribonucleotide,Oligodeoxynucleotides
D009843 Oligoribonucleotides A group of ribonucleotides (up to 12) in which the phosphate residues of each ribonucleotide act as bridges in forming diester linkages between the ribose moieties.
D000215 Acylation The addition of an organic acid radical into a molecule.
D013942 Thymine Nucleotides Phosphate esters of THYMIDINE in N-glycosidic linkage with ribose or deoxyribose, as occurs in nucleic acids. (From Dorland, 28th ed, p1154) Thymidine Phosphates,Nucleotides, Thymine,Phosphates, Thymidine
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D054303 HIV Reverse Transcriptase A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process. Reverse Transcriptase, HIV,Reverse Transcriptase, Human Immunodeficiency Virus,Transcriptase, HIV Reverse
D017931 DNA Primers Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques. DNA Primer,Oligodeoxyribonucleotide Primer,Oligodeoxyribonucleotide Primers,Oligonucleotide Primer,Oligonucleotide Primers,Primer, DNA,Primer, Oligodeoxyribonucleotide,Primer, Oligonucleotide,Primers, DNA,Primers, Oligodeoxyribonucleotide,Primers, Oligonucleotide
D018894 Reverse Transcriptase Inhibitors Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. Reverse Transcriptase Inhibitor,Inhibitors, Reverse Transcriptase,Inhibitor, Reverse Transcriptase,Transcriptase Inhibitor, Reverse
D019380 Anti-HIV Agents Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS. AIDS Drug,AIDS Drugs,Anti-AIDS Agents,Anti-AIDS Drug,Anti-HIV Agent,Anti-HIV Drug,Anti-AIDS Drugs,Anti-HIV Drugs,Agent, Anti-HIV,Agents, Anti-AIDS,Agents, Anti-HIV,Anti AIDS Agents,Anti AIDS Drug,Anti AIDS Drugs,Anti HIV Agent,Anti HIV Agents,Anti HIV Drug,Anti HIV Drugs,Drug, AIDS,Drug, Anti-AIDS,Drug, Anti-HIV,Drugs, AIDS,Drugs, Anti-AIDS,Drugs, Anti-HIV
D019384 Nucleic Acid Synthesis Inhibitors Compounds that inhibit cell production of DNA or RNA. DNA Polymerase Inhibitor,DNA Synthesis Inhibitor,DNA Synthesis Inhibitors,Nucleic Acid Synthesis Inhibitor,RNA Synthesis Inhibitor,RNA Synthesis Inhibitors,DNA Polymerase Inhibitors,Inhibitors, DNA Synthesis,Inhibitors, Nucleic Acid Synthesis,Inhibitors, RNA Synthesis,Inhibitor, DNA Polymerase,Inhibitor, DNA Synthesis,Inhibitor, RNA Synthesis,Inhibitors, DNA Polymerase,Polymerase Inhibitor, DNA,Polymerase Inhibitors, DNA,Synthesis Inhibitor, DNA,Synthesis Inhibitor, RNA,Synthesis Inhibitors, DNA,Synthesis Inhibitors, RNA

Related Publications

A Marx, and M Amacker, and M Stucki, and U Hübscher, and T A Bickle, and B Giese
Stereo-selectivity of HIV-1 reverse transcriptase toward isomers of thymidine-5'-O-1-thiotriphosphate.
July 2005, Protein science : a publication of the Protein Society,
A Marx, and M Amacker, and M Stucki, and U Hübscher, and T A Bickle, and B Giese
A comparison of the conformations of the 5'-triphosphates of zidovudine (AZT) and thymidine bound to HIV-1 reverse transcriptase.
March 1993, Biochemical and biophysical research communications,
A Marx, and M Amacker, and M Stucki, and U Hübscher, and T A Bickle, and B Giese
Inhibition of HIV-1 reverse transcriptase by 5'-triphosphates of 5-substituted uridine analogs.
December 1989, Antiviral research,
A Marx, and M Amacker, and M Stucki, and U Hübscher, and T A Bickle, and B Giese
Synthesis of nucleoside 5'-O-alpha,beta-methylene-beta-triphosphates and evaluation of their potency towards inhibition of HIV-1 reverse transcriptase.
March 2010, Organic & biomolecular chemistry,
A Marx, and M Amacker, and M Stucki, and U Hübscher, and T A Bickle, and B Giese
Introduction of the alpha-P-borano-group into deoxynucleoside triphosphates increases their selectivity to HIV-1 reverse transcriptase relative to DNA polymerases.
March 2003, Nucleosides, nucleotides & nucleic acids,
A Marx, and M Amacker, and M Stucki, and U Hübscher, and T A Bickle, and B Giese
Inhibition of multi-drug resistant HIV-1 reverse transcriptase by nucleoside β-triphosphates.
June 2011, Bioorganic & medicinal chemistry letters,
A Marx, and M Amacker, and M Stucki, and U Hübscher, and T A Bickle, and B Giese
Initial binding of 2'-deoxynucleoside 5'-triphosphates to human immunodeficiency virus type 1 reverse transcriptase.
October 1991, The Journal of biological chemistry,
A Marx, and M Amacker, and M Stucki, and U Hübscher, and T A Bickle, and B Giese
Inhibition of HIV reverse transcriptase by 2',3'-dideoxynucleoside triphosphates.
December 1987, Biochemical pharmacology,
A Marx, and M Amacker, and M Stucki, and U Hübscher, and T A Bickle, and B Giese
4'C-ethynyl-thymidine acts as a chain terminator during DNA-synthesis catalyzed by HIV-1 reverse transcriptase.
February 2005, Bioorganic & medicinal chemistry letters,
A Marx, and M Amacker, and M Stucki, and U Hübscher, and T A Bickle, and B Giese
Substrate mimicry: HIV-1 reverse transcriptase recognizes 6-modified-3'-azido-2',3'-dideoxyguanosine-5'-triphosphates as adenosine analogs.
January 2012, Nucleic acids research,
Copied contents to your clipboard!