A Stabilizing Influence: CAL PDZ Inhibition Extends the Half-Life of ΔF508-CFTR

被引：58
作者：
Cushing, Patrick R. [2 ]
Vouilleme, Lars [1 ]
Pellegrini, Maria [3 ]
Boisguerin, Prisca [1 ]
Madden, Dean R. [2 ]
机构：
[1] Charite, Inst Med Immunol, D-10115 Berlin, Germany
[2] Dartmouth Med Sch, Dept Biochem, Hanover, NH 03755 USA
[3] Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA
来源：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2010年 / 49卷 / 51期
关键词：
cystic fibrosis; epithelial cells; ion channels; PDZ domain; protein-protein interactions; TRANSMEMBRANE-CONDUCTANCE-REGULATOR; CYSTIC-FIBROSIS; CFTR; MEMBRANE; PROTEIN; TRAFFICKING; ASSOCIATION; EXPRESSION; MECHANISM;
D O I：
10.1002/anie.201005585
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
It pays to recycle! The most common mutation in cystic fibrosis (CF) impedes maturation and accelerates breakdown of the ion channel CFTR. A "stabilizer" has been characterized that blocks a PDZ domain responsible for CFTR degradation. The inhibitor iCAL36 extends the chloride channel's half-life in airway epithelial cells. It also complements the activity of a corrector of the maturation defect, thus suggesting the potential for combination CF therapies. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
引用
收藏
页码：9907 / 9911
页数：5
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