The Experts below are selected from a list of 258 Experts worldwide ranked by ideXlab platform

Mark Nelson - One of the best experts on this subject based on the ideXlab platform.

Sankaran Murugesan - One of the best experts on this subject based on the ideXlab platform.

  • Design and synthesis of tetrahydrophthalimide derivatives as inhibitors of HIV-1 Reverse Transcriptase
    Organic and Medicinal Chemistry Letters, 2013
    Co-Authors: Ashok Penta, Swastika Ganguly, Sankaran Murugesan
    Abstract:

    Background Non-nucleoside Reverse Transcriptase inhibitors (NNRTIs) are one of the key components in highly active anti-retroviral therapy because of their high specificity and less toxicity. NNRTIs inhibit Reverse Transcriptase enzyme by binding to the allosteric site, which is 10Å away from the active site. Rapid emergence of resistance is the major problem with all anti-HIV agents. Hence, there is continuous need to develop novel anti-HIV agents active against both drug sensitive and resistance strains. Results All the 16 synthesized 2-(1,3-dioxo-3a,4-dihydro-1 H -isoindol-2(3 H ,7 H ,7a H )-yl)- N -(substitutedphenyl) acetamide 4(a-p) analogs were characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectroscopy, and elemental analysis. Lipinski rule of five parameters and molecular parameters like solubility, drug likeness, and drug score were derived for designed analogs using online servers like Molinspiration and Osiris property explorer. Synthesized compounds were evaluated for their HIV-1 Reverse Transcriptase inhibitor activity by HIV-1 RNA-dependent DNA polymerase activity assay at 2 and 20 μM concentrations. Conclusions Among the 16 synthesized compounds, 4a , 4b , 4f , 4g , 4k , and 4l showed weak Reverse Transcriptase inhibitor activity at 20 μM concentration. For the designed compounds, there was no correlation observed between molecular modeling and in vitro studies.

C. Scott - One of the best experts on this subject based on the ideXlab platform.

Ashok Penta - One of the best experts on this subject based on the ideXlab platform.

  • Design and synthesis of tetrahydrophthalimide derivatives as inhibitors of HIV-1 Reverse Transcriptase
    Organic and Medicinal Chemistry Letters, 2013
    Co-Authors: Ashok Penta, Swastika Ganguly, Sankaran Murugesan
    Abstract:

    Background Non-nucleoside Reverse Transcriptase inhibitors (NNRTIs) are one of the key components in highly active anti-retroviral therapy because of their high specificity and less toxicity. NNRTIs inhibit Reverse Transcriptase enzyme by binding to the allosteric site, which is 10Å away from the active site. Rapid emergence of resistance is the major problem with all anti-HIV agents. Hence, there is continuous need to develop novel anti-HIV agents active against both drug sensitive and resistance strains. Results All the 16 synthesized 2-(1,3-dioxo-3a,4-dihydro-1 H -isoindol-2(3 H ,7 H ,7a H )-yl)- N -(substitutedphenyl) acetamide 4(a-p) analogs were characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectroscopy, and elemental analysis. Lipinski rule of five parameters and molecular parameters like solubility, drug likeness, and drug score were derived for designed analogs using online servers like Molinspiration and Osiris property explorer. Synthesized compounds were evaluated for their HIV-1 Reverse Transcriptase inhibitor activity by HIV-1 RNA-dependent DNA polymerase activity assay at 2 and 20 μM concentrations. Conclusions Among the 16 synthesized compounds, 4a , 4b , 4f , 4g , 4k , and 4l showed weak Reverse Transcriptase inhibitor activity at 20 μM concentration. For the designed compounds, there was no correlation observed between molecular modeling and in vitro studies.

Kathleen Collins - One of the best experts on this subject based on the ideXlab platform.

  • RNA Binding Domain of Telomerase Reverse Transcriptase
    Molecular and Cellular Biology, 2001
    Co-Authors: Cary K. Lai, James R. Mitchell, Kathleen Collins
    Abstract:

    Telomerase is a ribonucleoprotein Reverse Transcriptase that extends the ends of chromosomes. The two telomerase subunits essential for catalysis in vitro are the telomerase Reverse Transcriptase (TERT) and the telomerase RNA. Using truncations and site-specific mutations, we identified sequence elements of TERT and telomerase RNA required for catalytic activity and protein-RNA interaction for Tetrahymena thermophila telomerase. We found that the TERT amino and carboxyl termini, although evolutionarily poorly conserved, are nonetheless important for catalytic activity. In contrast, high-affinity telomerase RNA binding requires only a small region in the amino terminus of TERT. Surprisingly, the TERT region necessary and sufficient for telomerase RNA binding is completely separable from the Reverse Transcriptase motifs. The minimal Tetrahymena TERT RNA binding domain contains two sequence motifs with ciliate-specific conservation and one TERT motif with conservation across all species. With human TERT, we demonstrate that a similar region within the TERT amino terminus is essential for human telomerase RNA binding as well. Finally, we defined the Tetrahymena telomerase RNA sequences that are essential for TERT interaction. We found that a four-nucleotide region 5′ of the template is critical for TERT binding and that the 5′ end of telomerase RNA is sufficient for TERT binding. Our results reveal at least one evolutionarily conserved molecular mechanism by which the telomerase Reverse Transcriptase is functionally specialized for obligate use of an internal RNA template.

  • Template definition by Tetrahymena telomerase Reverse Transcriptase.
    The EMBO Journal, 2000
    Co-Authors: Michael C. Miller, Jesse K. Liu, Kathleen Collins
    Abstract:

    The ribonucleoprotein enzyme telomerase extends chromosome ends by copying a specific template sequence within its integral RNA component. An active recombinant telomerase RNP is minimally composed of this RNA and the telomerase Reverse Transcriptase (TERT) protein, which contains sequence motifs conserved among viral Reverse Transcriptases (RTs), flanked by N- and C-terminal extensions specific to TERTs. We have used site-directed mutagenesis to explore the roles of Tetrahymena TERT in determining features of telomerase activity in general and in establishing the boundaries and use of an internal RNA template in specific. We identify a new ciliate-specific motif in the TERT N-terminus required for template definition. Moreover, several residues in Reverse Transcriptase motifs 1, 2, A and D are critical for specific aspects of internal template use. Our results indicate that the unique specificity of telomerase activity is conferred to a Reverse Transcriptase active site by TERT residues both within and beyond the RT motif region.

  • The Reverse Transcriptase component of the Tetrahymena telomerase ribonucleoprotein complex
    Proceedings of the National Academy of Sciences of the United States of America, 1998
    Co-Authors: Kathleen Collins, Leena Gandhi
    Abstract:

    Telomerase is a eukaryotic Reverse Transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. We describe here the identification of a Tetrahymena telomerase protein with Reverse Transcriptase motifs, p133. This subunit is associated with the previously identified Tetrahymena telomerase RNA and the telomerase proteins p80 and p95 in immunoprecipitation assays. Therefore, all four known Tetrahymena telomerase components are present in a single complex. Expressed in rabbit reticulocyte lysate, recombinant p133 and telomerase RNA alone catalyze a Reverse Transcriptase activity with some similarities to and some differences from native Tetrahymena telomerase. These experiments suggest a complexity of telomerase structure and function.