MODIFIED ARGININE-CONTAINING LYTIC PEPTIDES AND METHOD OF MAKING THE SAME BY GLYOXYLATION

摘要

A non-neurotoxin, arginine residue-containing non-naturally occurring lytic peptide comprising a sequence of amino acid residues in sufficient number and arrangement to confer lytic activity to the peptide, wherein the guanido groups of the arginine residues and the α-amino group of the N-terminal amino acid are sufficiently glyoxylated to impart enhanced tryptic, chymotryptic, and aminopeptidase digestion resistance to peptide. The compositions of the invention are suitable for in vivo administration. A method of making the same, to impart enhanced tryptic digestion resistance thereto, comprising glyoxylating the guanido groups of the arginine residues and the α-amino group of the N-terminal amino acid with glyoxal in the presence of a pyridine containing a buffer for sufficient time and at sufficient conditions to glyoxylate the side chain and α-amino groups to sufficient extent to confer enhanced proteolytic digestion resistance to the peptide.