DESIGN, SYNTHESIS, AND CHARACTERIZATION OF A CATIONIC PEPTIDE THAT BINDS TO NUCLEIC-ACIDS AND PERMEABILIZES BILAYERS

We have designed a cationic amphipathic peptide, KALA (WEAKLAKALAKALAK HLAKALAKALKACEA), that binds to DNA, destabilizes membranes, and media tes DNA transfection. KALA undergoes a pH-dependent random coil to amp hipathic or-helical conformational change as the pH is increased from 5.0 to 7.5. One face displays hydrophobic leucine residues, and the op posite face displays hydrophilic lysine residues. KALA-mediated releas e of entrapped aqueous contents from neutral and negatively charged li posomes increases with increasing helical content. KALA binds to oligo nucleotides or plasmid DNA and retards their migration in gel electrop horesis. It displaces 50% of ethidium bromide from DNA at a charge rat io (+/-) of 0.9/1. In cultured cells, KALA assists oligonucleotide nuc lear delivery when complexes are prepared at a 10/1 (+/-) charge ratio . KALA/DNA (10/1) (+/-) complexes mediate transfection of a variety of cell lines. The KALA sequence provides a starting point for a family of peptides that incorporate other functions to improve DNA delivery s ystems.