Polymyxin B analogs for LPS detoxification

摘要

The invention relates to SAEP II peptide dimers that mimic polymyxin B i . a . in its ability to bind non-covalently the lipopolysaccharide (LPS) of Gram-negative bacteria with high affinity, and therefore to detoxify LPS as polymyxin B does. The dimeric structure is maintained by a pair of disulphide bonds involving the two cystein residues present in the peptide sequence, which does not exceed 17 amino acids and essentially comprises cationic and hydrophobic amino acid residues. The invention also relates to a novel polymyxin B analog (SAEP2-L2), which is a peptide of formula NH2-Lys-Thr-Lys-Cys1-Lys-Phe-Leu-Leu-Leu-Cys2-COOH. This peptide, either in a monomeric or dimeric form, is also able to detoxify LPS. In the dimers of the invention, peptides may have a parallel or anti-parallel orientation. SAEP II dimers and the SAEP2-L2 peptide are useful for treating or preventing septic shock and related disorders generated by Gram-negative bacteria infection. The invention also relates to LPS-peptide complexes in which LPS and SAEP II dimers or peptide SAEP2-L2 are non-covalently bound together. These complexes are useful as vaccinal agents against Gram-negative bacteria infection.