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Discovery of a Small-Molecule Probe for V-ATPase Function.

ABSTRACT: Lysosomes perform a critical cellular function as a site of degradation for diverse cargoes including proteins, organelles, and pathogens delivered through distinct pathways, and defects in lysosomal function have been implicated in a number of diseases. Recent studies have elucidated roles for the lysosome in the regulation of protein synthesis, metabolism, membrane integrity, and other processes involved in homeostasis. Complex small-molecule natural products have greatly contributed to the investigation of lysosomal function in cellular physiology. Here we report the discovery of a novel, small-molecule modulator of lysosomal acidification derived from diversity-oriented synthesis through high-content screening.

SUBMITTER: Aldrich LN

PROVIDER: S-EPMC4416280 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Discovery of a Small-Molecule Probe for V-ATPase Function.

Aldrich Leslie N LN Kuo Szu-Yu SY Castoreno Adam B AB Goel Gautam G Kuballa Petric P Rees Matthew G MG Seashore-Ludlow Brinton A BA Cheah Jaime H JH Latorre Isabel J IJ Schreiber Stuart L SL Shamji Alykhan F AF Xavier Ramnik J RJ

Journal of the American Chemical Society 20150420 16

Lysosomes perform a critical cellular function as a site of degradation for diverse cargoes including proteins, organelles, and pathogens delivered through distinct pathways, and defects in lysosomal function have been implicated in a number of diseases. Recent studies have elucidated roles for the lysosome in the regulation of protein synthesis, metabolism, membrane integrity, and other processes involved in homeostasis. Complex small-molecule natural products have greatly contributed to the in ...[more]

PMID: 25860544

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