主权项 |
1. A peptide for use as a medicament in the treatment of an infection with gram-positive bacteria comprising an amino acid sequence according to the general formula A or B:
X1—N2—X2—X3—P5—V6—Y7—I8—P9—X4—X5—R12—P13—P14—H15—P16 (Formula A) X1—N2—X2—X3—P5—V6—Y7—I8—P9—X4—X5—R12—P13—P14—H15—P16—X6—X7 (Formula B) wherein the amino acid sequence according to formula A or B has at least 60%, preferably at least 70%, preferably at least 80% amino acid sequence identity to the native Apidaecin 1b according to SEQ ID NO: 2 and wherein: X1 is selected from nonpolar, aromatic, positively charged amino acid residues, amino acid residues with a thiol group, amino acid residues with a selenol group, proline and proline derivatives; N2, X2 and P5 are selected independently from each other from neutral and positively charged amino acid residues; X3 is selected from positively charged amino acid residues, amino acid residues with a thiol group and amino acid residues with a selenol group; V6 is selected from nonpolar amino acid residues with at least 2 C atoms in the side chain, aromatic amino acid residues, positively charged amino acid residues, amino acid residues with a thiol group, amino acid residues with a selenol group, proline and proline derivatives; Y7 is selected from tyrosine, positively charged amino acid residues, amino acid residues with a thiol group and amino acid residues with a selenol group; I8 is selected from nonpolar, aromatic amino acid residues with at least 2 and at most 8 C atoms in the side chain, positively charged amino acid residues, amino acid residues with a thiol group and amino acid residues with a selenol group; P9, P13, P14 and P16 are selected independently of each other from positively charged amino acid residues, amino acid residues with a thiol group, amino acid residues with a selenol group, nonpolar aromatic amino acid residues, heteroaromatic amino acid residues, proline and proline derivatives; X4 is selected from neutral, positively charged amino acid residues, amino acid residues with a thiol group and amino acid residues with a selenol group; X5 is selected from proline, proline derivatives, positively charged amino acid residues, amino acid residues with a thiol group and amino acid residues with a selenol group; R12 is a positively charged amino acid residue; H15 is selected from histidine, positively charged amino acid residues, amino acid residues with a thiol group and amino acid residues with a selenol group; X6 is selected from positively charged amino acid residues; X7 is selected from nonpolar amino acid residues, positively charged amino acid residues, amino acid residues with a thiol group and amino acid residues with a selenol group, characterised in that at least one of the positions 2, 5 to 11, 13 to 16 and 18 of SEQ ID NO: 2 is modified, so that at least one of the following conditions applies to the peptide according to formula A or B:
N2 is selected from nonpolar amino acid residues, positively charged amino acid residues, amino acid residues with a thiol group and amino acid residues with a selenol group, preferably N2 is selected from tryptophan, arginine and cysteine,X4 is selected from lysine, δ-hydroxylysine, ε-N-methyllysine, allo-hydroxylysine, cysteine and selenol-cysteine,at least one of the residues selected from P5, V6, Y7, I8, P9, P11, P13, P14, P16 and X7 is a positively charged residue, an amino acid residue with a thiol group or an amino acid residue with a selenol group, and/orH15 is selected from amino acid residues with a thiol group and amino acid residues with a selenol group, preferably H15 is a cysteine. |