The Experts below are selected from a list of 1776 Experts worldwide ranked by ideXlab platform

Paul R Thompson - One of the best experts on this subject based on the ideXlab platform.

  • Development of a Suicide Inhibition-Based Protein Labeling Strategy for Nicotinamide N-Methyltransferase
    ACS Chemical Biology, 2019
    Co-Authors: Santanu Mondal, Ari J. Salinger, Walter Fast, Li Zheng, Eranthie Weerapana, Paul R Thompson
    Abstract:

    Nicotinamide N-methyltransferase (NNMT) catalyzes the S-adenosyl-l-methionine-dependent methylation of nicotinamide to form N-methylnicotinamide. This enzyme detoxifies xenobiotics and regulates NAD+ biosynthesis. Additionally, NNMT is overexpressed in various cancers. Herein, we describe the first NNMT-targeted Suicide substrates. These compounds, which include 4-chloropyridine and 4-chloronicotinamide, exploit the broad substrate scope of NNMT; methylation of the pyridine nitrogen enhances the electrophilicity of the C4 position, thereby promoting an aromatic nucleophilic substitution by C159, a noncatalytic cysteine. On the basis of this activity, we developed a Suicide Inhibition-based protein labeling strategy using an alkyne-substituted 4-chloropyridine that selectively labels NNMT in vitro and in cells. In total, this study describes the first NNMT-directed activity-based probes.

  • Development of a Suicide Inhibition-Based Protein Labeling Strategy for Nicotinamide N‑Methyltransferase
    2019
    Co-Authors: Sudeshna Sen, Ari J. Salinger, Walter Fast, Santanu Mondal, Li Zheng, Eranthie Weerapana, Paul R Thompson
    Abstract:

    Nicotinamide N-methyltransferase (NNMT) catalyzes the S-adenosyl-l-methionine-dependent methylation of nicotinamide to form N-methylnicotinamide. This enzyme detoxifies xenobiotics and regulates NAD+ biosynthesis. Additionally, NNMT is overexpressed in various cancers. Herein, we describe the first NNMT-targeted Suicide substrates. These compounds, which include 4-chloropyridine and 4-chloronicotinamide, exploit the broad substrate scope of NNMT; methylation of the pyridine nitrogen enhances the electrophilicity of the C4 position, thereby promoting an aromatic nucleophilic substitution by C159, a noncatalytic cysteine. On the basis of this activity, we developed a Suicide Inhibition-based protein labeling strategy using an alkyne-substituted 4-chloropyridine that selectively labels NNMT in vitro and in cells. In total, this study describes the first NNMT-directed activity-based probes

Santanu Mondal - One of the best experts on this subject based on the ideXlab platform.

  • Development of a Suicide Inhibition-Based Protein Labeling Strategy for Nicotinamide N-Methyltransferase
    ACS Chemical Biology, 2019
    Co-Authors: Santanu Mondal, Ari J. Salinger, Walter Fast, Li Zheng, Eranthie Weerapana, Paul R Thompson
    Abstract:

    Nicotinamide N-methyltransferase (NNMT) catalyzes the S-adenosyl-l-methionine-dependent methylation of nicotinamide to form N-methylnicotinamide. This enzyme detoxifies xenobiotics and regulates NAD+ biosynthesis. Additionally, NNMT is overexpressed in various cancers. Herein, we describe the first NNMT-targeted Suicide substrates. These compounds, which include 4-chloropyridine and 4-chloronicotinamide, exploit the broad substrate scope of NNMT; methylation of the pyridine nitrogen enhances the electrophilicity of the C4 position, thereby promoting an aromatic nucleophilic substitution by C159, a noncatalytic cysteine. On the basis of this activity, we developed a Suicide Inhibition-based protein labeling strategy using an alkyne-substituted 4-chloropyridine that selectively labels NNMT in vitro and in cells. In total, this study describes the first NNMT-directed activity-based probes.

  • Development of a Suicide Inhibition-Based Protein Labeling Strategy for Nicotinamide N‑Methyltransferase
    2019
    Co-Authors: Sudeshna Sen, Ari J. Salinger, Walter Fast, Santanu Mondal, Li Zheng, Eranthie Weerapana, Paul R Thompson
    Abstract:

    Nicotinamide N-methyltransferase (NNMT) catalyzes the S-adenosyl-l-methionine-dependent methylation of nicotinamide to form N-methylnicotinamide. This enzyme detoxifies xenobiotics and regulates NAD+ biosynthesis. Additionally, NNMT is overexpressed in various cancers. Herein, we describe the first NNMT-targeted Suicide substrates. These compounds, which include 4-chloropyridine and 4-chloronicotinamide, exploit the broad substrate scope of NNMT; methylation of the pyridine nitrogen enhances the electrophilicity of the C4 position, thereby promoting an aromatic nucleophilic substitution by C159, a noncatalytic cysteine. On the basis of this activity, we developed a Suicide Inhibition-based protein labeling strategy using an alkyne-substituted 4-chloropyridine that selectively labels NNMT in vitro and in cells. In total, this study describes the first NNMT-directed activity-based probes

željko M Svedružic - One of the best experts on this subject based on the ideXlab platform.

  • in silico design of the first dna independent mechanism based inhibitor of mammalian dna methyltransferase dnmt1
    PLOS ONE, 2017
    Co-Authors: Vedran Miletic, Ivica Odorcic, Patrik Nikolic, željko M Svedružic
    Abstract:

    Background: Inhibitors of DNA methylation can be used to control functional organization of human genome in basic research and regenerative medicine. Results: We describe a set of adenosyl-1-methyl-pyrimidin-2-one derivatives as novel mechanism-based Suicide-inhibitors of mammalian DNA methyltransferase DNMT1. The inhibitors are designed to act as transition state analogs that can bind simultaneously to the cofactor binding site and the active site on DNMT1. The two binding sites and the mechanism-based Suicide-Inhibition are combined to provide highly potent and highly specific Inhibition. The stability of presented DNMT1-inhibitor complex is described in detail using 58 modifications that affect flexibility and binding interactions at specific sites within the complex. Conclusions: Presented results can guide synthesis and optimization of some highly specific mechanism-based inhibitors of mammalian DNA methylation with specific pharmacological properties.

Ari J. Salinger - One of the best experts on this subject based on the ideXlab platform.

  • Development of a Suicide Inhibition-Based Protein Labeling Strategy for Nicotinamide N-Methyltransferase
    ACS Chemical Biology, 2019
    Co-Authors: Santanu Mondal, Ari J. Salinger, Walter Fast, Li Zheng, Eranthie Weerapana, Paul R Thompson
    Abstract:

    Nicotinamide N-methyltransferase (NNMT) catalyzes the S-adenosyl-l-methionine-dependent methylation of nicotinamide to form N-methylnicotinamide. This enzyme detoxifies xenobiotics and regulates NAD+ biosynthesis. Additionally, NNMT is overexpressed in various cancers. Herein, we describe the first NNMT-targeted Suicide substrates. These compounds, which include 4-chloropyridine and 4-chloronicotinamide, exploit the broad substrate scope of NNMT; methylation of the pyridine nitrogen enhances the electrophilicity of the C4 position, thereby promoting an aromatic nucleophilic substitution by C159, a noncatalytic cysteine. On the basis of this activity, we developed a Suicide Inhibition-based protein labeling strategy using an alkyne-substituted 4-chloropyridine that selectively labels NNMT in vitro and in cells. In total, this study describes the first NNMT-directed activity-based probes.

  • Development of a Suicide Inhibition-Based Protein Labeling Strategy for Nicotinamide N‑Methyltransferase
    2019
    Co-Authors: Sudeshna Sen, Ari J. Salinger, Walter Fast, Santanu Mondal, Li Zheng, Eranthie Weerapana, Paul R Thompson
    Abstract:

    Nicotinamide N-methyltransferase (NNMT) catalyzes the S-adenosyl-l-methionine-dependent methylation of nicotinamide to form N-methylnicotinamide. This enzyme detoxifies xenobiotics and regulates NAD+ biosynthesis. Additionally, NNMT is overexpressed in various cancers. Herein, we describe the first NNMT-targeted Suicide substrates. These compounds, which include 4-chloropyridine and 4-chloronicotinamide, exploit the broad substrate scope of NNMT; methylation of the pyridine nitrogen enhances the electrophilicity of the C4 position, thereby promoting an aromatic nucleophilic substitution by C159, a noncatalytic cysteine. On the basis of this activity, we developed a Suicide Inhibition-based protein labeling strategy using an alkyne-substituted 4-chloropyridine that selectively labels NNMT in vitro and in cells. In total, this study describes the first NNMT-directed activity-based probes

Walter Fast - One of the best experts on this subject based on the ideXlab platform.

  • Development of a Suicide Inhibition-Based Protein Labeling Strategy for Nicotinamide N-Methyltransferase
    ACS Chemical Biology, 2019
    Co-Authors: Santanu Mondal, Ari J. Salinger, Walter Fast, Li Zheng, Eranthie Weerapana, Paul R Thompson
    Abstract:

    Nicotinamide N-methyltransferase (NNMT) catalyzes the S-adenosyl-l-methionine-dependent methylation of nicotinamide to form N-methylnicotinamide. This enzyme detoxifies xenobiotics and regulates NAD+ biosynthesis. Additionally, NNMT is overexpressed in various cancers. Herein, we describe the first NNMT-targeted Suicide substrates. These compounds, which include 4-chloropyridine and 4-chloronicotinamide, exploit the broad substrate scope of NNMT; methylation of the pyridine nitrogen enhances the electrophilicity of the C4 position, thereby promoting an aromatic nucleophilic substitution by C159, a noncatalytic cysteine. On the basis of this activity, we developed a Suicide Inhibition-based protein labeling strategy using an alkyne-substituted 4-chloropyridine that selectively labels NNMT in vitro and in cells. In total, this study describes the first NNMT-directed activity-based probes.

  • Development of a Suicide Inhibition-Based Protein Labeling Strategy for Nicotinamide N‑Methyltransferase
    2019
    Co-Authors: Sudeshna Sen, Ari J. Salinger, Walter Fast, Santanu Mondal, Li Zheng, Eranthie Weerapana, Paul R Thompson
    Abstract:

    Nicotinamide N-methyltransferase (NNMT) catalyzes the S-adenosyl-l-methionine-dependent methylation of nicotinamide to form N-methylnicotinamide. This enzyme detoxifies xenobiotics and regulates NAD+ biosynthesis. Additionally, NNMT is overexpressed in various cancers. Herein, we describe the first NNMT-targeted Suicide substrates. These compounds, which include 4-chloropyridine and 4-chloronicotinamide, exploit the broad substrate scope of NNMT; methylation of the pyridine nitrogen enhances the electrophilicity of the C4 position, thereby promoting an aromatic nucleophilic substitution by C159, a noncatalytic cysteine. On the basis of this activity, we developed a Suicide Inhibition-based protein labeling strategy using an alkyne-substituted 4-chloropyridine that selectively labels NNMT in vitro and in cells. In total, this study describes the first NNMT-directed activity-based probes