发明名称 MODIFIED APIDAECIN DERIVATIVES AS ANTIBIOTIC PEPTIDES
摘要 This invention relates to modified antibiotic peptides, particularly for use in medicine. The invention further relates to compositions and methods for destroying microorganisms, such as bacteria, viruses or fungi, and to methods for treating microbial infections. The object of the invention is to develop novel antibiotic peptides, particularly having enhanced antibiotic activity and an expanded spectrum of activity against other strains of bacteria, particularly gram-positive bacteria such as Staphylococcus aureus. ;According to the invention, the object is attained in a first aspect by a peptide according to claim 1.
申请公布号 US2015344524(A1) 申请公布日期 2015.12.03
申请号 US201214346624 申请日期 2012.09.21
申请人 Universitaet Leipzig 发明人 Hoffmann Ralf;Knappe Daniel;Hilpert Kai;Mikut Ralf;Ruden Serge
分类号 C07K7/08 主分类号 C07K7/08
代理机构 代理人
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.
地址 Leipzig DE
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