"We hope that this study will pave the way for a new class of peptide-based channel inhibitors that can help reverse the mucus dehydration seen in Cystic Fibrosis and COPD," said Robert Tarran, Ph.D., a researcher involved in the work from the Cystic Fibrosis/Pulmonary Research and Treatment Center at the University of North Carolina in Chapel Hill. "This would help restore mucus clearance and kick-start the lung's ability to clear unwanted pathogens."
To identify which part of SPLUNC1 actually affects ENaC, scientists eliminated parts of the protein until it lost function. In fact, even after the eliminating 85 percent of SPLUNC1, it still affected ENaC, suggesting that the ENaC inhibitory domain was in the remaining 15 percent. Researchers then synthesized an 18-amino acid peptide of this region and tested its ability to bind to ENaC and to inhibit fluid absorption in human bronchial epithelial cells derived from people with and without cystic fibrosis.