Synthetic macromolecular channel assembly for transport of chloride ions

Abstract

The present invention is directed to multiple-peptide channel assemblies for transport of anions such as chloride ions through epithelial cells, synthetic peptides capable of forming such channel assemblies and methods for using channel assemblies in therapeutic contexts for altering the flux of water across epithelial cells. The channel assemblies are composed of a plurality of peptides that transport through the membrane of an epithelial cell and provide for alteration of the flux of water through the cell. The peptides are soluble in water to a level of at least 10 mM and exhibit at least about 50% helical content when dispersed in a 40% trifluoroethanol/60% water solution. The peptides ideally have the amino acid sequence ABC(X).sub.n DEF, where A, B, C, D, F and X are individual amino acid residues, n ranges from 12-24 and at least one of the amino acids selected from the group consisting of A, B, and C is a charged amino acid, and at least one of the amino acids selected from the group consisting of D, E, and F is a charged amino acid. The method hereof provides for altering flux of water from an epithelial cell and includes providing from 3-6 peptides capable of forming a channel assembly with each of such peptides having from about 18-30 amino acid residues therein, then contacting the peptides with a surface of an epithelial cell to cause the peptides to embed therein and alter the flux of water across the cell.