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

被引：34

作者：

Adrich, Leslie N. ^{[1
,2
]}

Kuo, Szu-Yu ^{[2
,3
]}

Castoreno, Adam B. ^{[2
]}

Goel, Gautam ^{[4
,5
,6
]}

Kuballa, Petric ^{[4
,5
,6
]}

Rees, Matthew G. ^{[2
]}

Seashore-Ludlow, Brinton A. ^{[2
]}

Cheah, Jaime H. ^{[2
]}

Latorre, Isabel J. ^{[2
]}

Schreiber, Stuart L. ^{[1
,2
,7
]}

Shamji, Alykhan F. ^{[2
]}

Xavier, Ramnik J. ^{[4
,5
,6
]}

机构：

[1] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA

[2] Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA

[3] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

[4] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA

[5] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA

[6] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA

[7] Broad Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2015年 / 137卷 / 16期

基金：

美国国家卫生研究院;

关键词：

LYSOSOMAL MEMBRANE-PROTEINS; VACUOLAR H+-ATPASE; BUILD/COUPLE/PAIR STRATEGY; TUBULAR-ACIDOSIS; AMINO-ACIDS; AUTOPHAGY; INHIBITORS; IMMUNITY; INFLAMMATION; CHOLESTEROL;

D O I：

10.1021/jacs.5b02150

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：5563 / 5568

页数：6

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