Potential Agents for Treating Cystic Fibrosis: Cyclic Tetrapeptides that Restore Trafficking and Activity of ΔF508-CFTR.

ABSTRACT: Cystic fibrosis (CF) is a loss-of-function disease caused by mutations in the CF transmembrane conductance regulator (CFTR) protein, a chloride ion channel that localizes to the apical plasma membrane of epithelial cells. The most common form of the disease results from the deletion of phenylalanine-508 (ΔF508), leading to the accumulation of CFTR in the endoplasmic reticulum with a concomitant loss of chloride flux. We discovered that cyclic tetrapeptides, such as 11, 14, and 15, are able to correct the trafficking defect and restore cell surface activity of ΔF508-CFTR. Although this class of cyclic tetrapeptides is known to contain inhibitors of certain histone deacetylase (HDAC) isoforms, their HDAC inhibitory potencies did not directly correlate with their ability to rescue ΔF508-CFTR.

SUBMITTER: Hutt DM 

PROVIDER: S-EPMC3187562 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature