Antimicrobial peptides
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsCarol Clayberger, Alan M. Krensky
Life of this patent
Estimating the term…
Abstract
Artificial antimicrobial peptides are obtained by alterations in alpha helical portions of a known antimicrobial protein, granulysin. The peptides obtained have significantly improved antimicrobial activity and lack the ability to lyse mammalian cells, which may be toxic to a host. The peptides may be designed according to certain guidelines, and may further be modified by the addition of altered residues and alterations in normal peptide secondary and tertiary structure, including modifications in quaternary (multimeric) structure.
Claims23
An artificial antimicrobial peptide having:
- at least 90% sequence identity to peptide G11.46 (SEQ ID NO:
- 93), G12.21 (SEQ ID NO:
- 64) or G14.15 (SEQ ID NO:
- 83), but further having at least one non-identical amino acid when compared to SEQ ID NO:
- 2, an MIC against at least one of a pathogenic bacterium selected from the group consisting of E. coli, S. typhimurium and B. cereus of less than 10 μM;
- and
- having minimal lytic activity against mammalian cells.
An artificial antimicrobial peptide selected from the group consisting of:
- G8.17, (SEQ ID NO:
- 9), G8.3, (SEQ ID NO:
- 12), G8.15, (SEQ ID NO:
- 13), G8.11, (SEQ ID NO:
- 18), G11.6, (SEQ ID NO:
- 16), G11.3, (SEQ ID NO:
- 26), G11.24, (SEQ ID NO:
- 26), G11.30, (SEQ ID NO:
- 39), G11.32, (SEQ ID NO:
- 41), G11.34, (SEQ ID NO:
- 26), G11.35, (SEQ ID NO:
- 48), G11.55, (SEQ ID NO:
- 35), G11.46, (SEQ ID NO:
- 93), G12.5, (SEQ ID NO:
- 51), G12.10, (SEQ ID NO:
- 61), G12.19, (SEQ ID NO:
- 65), G12.20, (SEQ ID NO:
- 66), G12.21, (SEQ ID NO:
- 64), G14.2, (SEQ ID NO:
- 81), G14.10, (SEQ ID NO:
- 81), G14.11, (SEQ ID NO:
- 83), and G14.15 (SEQ ID NO:
- 83), wherein said peptide has an MIC (μM) in at least two microbial organisms selected from the group consisting of:
- E. coli, S. typhimurium, V. cholerae and B. cereus of less than about 2.0, and further has minimal lysis of mammalian cells.
A method for preparing an antimicrobial peptide, comprising:
- (a) selecting a sequence of between 10 and 20 residues comprised in SEQ ID NO:
- 2;
- (b) modifying the sequence by increasing a selected number of charged residues to be at least 8 residues;
- (c) modifying the sequence to include at least one D-amino acid;
- (d) preparing the peptide;
- (e) testing the peptide for antimicrobial activity against at least 3 microorganisms and selecting only a peptide with an MIC less than 1.0 μM against at least one of the microorganisms, and selecting as the antimicrobial peptide one having at least 90% sequence identity to peptide G11.46, (SEQ ID NO:
- 93), G12.21 (SEQ ID NO:
- 64), or 90% sequence identity to G14.15 (SEQ ID NO:
- 83), having at least one non-identical amino acid when compared to SEQ ID NO:
- 2 and having minimum lytic activity against mammalian cells.
Dependencies are inferred from the claim text.