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Project Summary Post-translational modifications (PTMs) of proteins are involved in virtually all cellular signaling pathways. Pharmacological intervention in these events is an important strategy for drug development. In this project, we propose to establish a novel platform for the discovery of covalent inhibitors of cysteine post-translational modifications, in particular, the prenylation of the C-termini of H-Ras and K-Ras. These events are critical for oncogenic mutants of these proteins to drive cell uncontrolled growth and division. In contrast to typical strategies for blocking PTMs, we will screen for non-peptidic macrocycles that bind covalently to the modified epitope on the substrate protein (H-Ras or K-Ras), rather than compounds that target the modifying enzyme. In this way, we believe it will be possible to manipulate single PTMs with unprecedented selectivity.
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2-Pyridone Formation: An Efficient Method for the Solid-Phase Synthesis of Homodimers.
2-吡啶酮形成:同二聚体固相合成的有效方法。
DOI: 10.1002/chem.202302937
发表时间: 2024
期刊: Chemistry (Weinheim an der Bergstrasse, Germany)
影响因子: --
作者: [Abboud,SkanderA, Kodadek,Thomas]
通讯作者: Kodadek,Thomas
Establishment of a Cell-Based Screening Platform for DNA Encoded Libraries
  • 批准号:
    10646635
  • 项目类别:
  • 资助金额:
    $33.81万
  • 财政年份:
    2023
  • 负责人:
    Thomas J. Kodadek
  • 依托单位:
Phenotypic screening using DNA-encoded libraries
  • 批准号:
    10238888
  • 项目类别:
  • 资助金额:
    $59.51万
  • 财政年份:
    2018
  • 负责人:
    Thomas J. Kodadek
  • 依托单位:
Phenotypic screening using DNA-encoded libraries
  • 批准号:
    10622655
  • 项目类别:
  • 资助金额:
    $18.12万
  • 财政年份:
    2018
  • 负责人:
    Thomas J. Kodadek
  • 依托单位:
Phenotypic screening using DNA-encoded libraries
  • 批准号:
    10001013
  • 项目类别:
  • 资助金额:
    $77.15万
  • 财政年份:
    2018
  • 负责人:
    Thomas J. Kodadek
  • 依托单位:
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