Lytic peptides with amphipathic alpha helices and positively charged N- or C-terminal, methods of activation/inactivation, compositions and methods of treatment are also included

摘要

A molecule which has lytic activity, comprising an amphipathic á-helical peptide in which the hydrophilic face of the á-helix comprises at least two amino acids each of which has a net positive charge, and in which the molecule has an overall positive charge of two. The amphipathic á-helix has the general formula 1 or 2 where Ù is glycine; hydrophobic amino acid including but not limited to alanine, isoleucine, leucine, valine and norleucine or Ö Ö phenylalanine, tryptophan, tyrosine, a nonnaturally occurring aromatic amino acid, or a synthetic aromatic residue; C is cysteine or cysteine amide P is proline Hypro is hydroxyproline Z is an amino acid which is not negatively charged, or is either crosslinked agent, or a blocking agent and X is a sequence of hydrophilic amino acids, at least one of which is a basic amino acid and where C or Z may be at either end of the peptide not at both ends. Further claimed is the method of modulating lytic activity of these molecules, and the use to treat cancer, HIV manifestation, viral infection and microbial infection.