Nonclassical transport proteins and peptides: An alternative to classical macromolecule delivery systems

The number of peptides and proteins known to exhibit nonclassical transport activity has increased significantly in recent years. In most cases, these entities have been studied in relation to their ability to deliver high molecular weight compounds, including proteins and DNA, for the ultimate purpose of developing new drug delivery strategies. In this review, an overview of the various types of vectors is presented. The in vitro and in vivo delivery successes of this technology, as well as preliminary therapeutic efforts, are described. Although a comprehensive mechanism of nonclassical transport has not yet been clearly established, we propose a straightforward model based on the cationic nature of the vectors and the need for lack of highly organized structure. In this hypothesis we suggest that the movement of polycations is mediated by a network of extra- and intracellular polyanions while transport across the bilayer is facilitated by cation-pi interactions between the vectors' basic groups and aromatic amino acid side chains in the bilayer spanning helices of membrane proteins. (C) 2003 Wiley-Liss, Inc. and the American Pharmacists Association.