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A library approach to rapidly discover photoaffinity probes of the mRNA decapping scavenger enzyme DcpS

机译:快速发现mRNA脱盖清除剂DcpS的光亲和探针的文库方法

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摘要

Despite its diverse applications, such as identification of the protein binding partners of small molecules and investigation of intra-cellular drug-target engagement, photoaffinity labelling (PAL) is intrinsically challenging, primarily due to the difficulty in discovering functionally active photoaffinity probes. Here we describe the creation of a chemoproteomic library to discover a novel photoaffinity probe for DcpS, an mRNA decapping enzyme that is a putative target for Spinal Muscular Atrophy. This library approach expedites the discovery of photoaffinity probes and expands the chemical biology toolbox to include RNA cap-binding proteins.
机译:尽管有多种应用,例如鉴定小分子的蛋白质结合伴侣和研究细胞内药物与靶标的结合,但光亲和标记(PAL)仍然具有内在挑战性,主要是因为难以发现具有功能活性的光亲和探针。在这里,我们描述了一个化学文库的创建,以发现DcpS的新型光亲和探针,DcpS是一种假定的靶标,它是脊髓性肌萎缩的靶标,是一种mRNA脱盖酶。该文库方法加快了光亲和探针的发现,并扩展了化学生物学工具箱,使其包含RNA帽结合蛋白。

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  • 来源
    《Molecular BioSystems》 |2015年第10期|2709-2712|共4页
  • 作者单位

    Worldwide Medicinal Chemistry, Pfizer Inc., 610 Main Street, Cambridge, MA 02139, USA;

    Worldwide Medicinal Chemistry, Pfizer Inc., 610 Main Street, Cambridge, MA 02139, USA;

    Worldwide Medicinal Chemistry, Pfizer Inc., 610 Main Street, Cambridge, MA 02139, USA;

    Worldwide Medicinal Chemistry, Pfizer Inc., Eastern Point Road, Groton CT, 06340, USA;

    Structural Biology and Biophysics, Worldwide Medicinal Chemistry, Pfizer Inc., Eastern Point Road, Groton CT, 06340, USA;

    Worldwide Medicinal Chemistry, Pfizer Inc., Eastern Point Road, Groton CT, 06340, USA;

    Primary Pharmacology Group, Pfizer Inc., Eastern Point Road, Groton CT, 06340, USA;

    Worldwide Medicinal Chemistry, Pfizer Inc., 610 Main Street, Cambridge, MA 02139, USA;

    Worldwide Medicinal Chemistry, Pfizer Inc., Eastern Point Road, Groton CT, 06340, USA;

    Worldwide Medicinal Chemistry, Pfizer Inc., 610 Main Street, Cambridge, MA 02139, USA;

    Rare Disease Research Unit, Pfizer Inc., Cambridge, MA 02139, USA;

    Worldwide Medicinal Chemistry, Pfizer Inc., 610 Main Street, Cambridge, MA 02139, USA;

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