CONFORMATIONAL STRUCTURE OF THE AMPHIPATHIC PEPTIDE INSECTICIDE L-KALA

The conformation structure of the tetrapeptide Ac-Lys-Ala-Leu-Ala-OMe, the repeat unit of a 30 residue peptide YAA(KALA)(6)LAA, and also its analog containing an unusual amino acid, (Aib): Ac-Lys-Aib-Leu-Aib-OM e, has been investigated by the PCILO method. The global/low-energy mi nima for all the residues Lies at phi = -30 degrees and psi = 120 degr ees. In this conformation, the potential hydrogen-bonding sites are fr ee, i.e., capable of intermolecular hydrogen bonding. As the angles li e closer to the collagen helical region and potential hydrogen-bonding sites are free, this structure is named the collagen-type helix. In a queous solution, this structure is stabilized by solvation of the pept ide bond. The local-energy minimum in all maps correspond to the right -handed helical region. The helix thus formed generates a pore of 3 An gstrom along the helix axis, with one lateral hydrophobic side and the other hydrophilic side. The pore thus formed is cation-selective and accounts for the leakage of contents from vesicles. On the basis of th e length of the helix and placement of the side chains of lysine and l eucine, a model has been proposed for the aggregation and fusion of th e vesicles. The amphipathic basic residues interact with the head grou ps of the acidic liposomes by extending toward the polar face of the h elix to insert their charged moieties by overcoming the electrostatic repulsive forces between the opposing vesicles. (C) 1995 John Wiley an d Sons, Inc.