Antimicrobial cationic peptides

• US 6,191,254 B1
• Filed: 08/23/1996
• Issued: 02/20/2001
• Est. Priority Date: 08/23/1995
• Status: Expired due to Fees

• Current Assignee: University of British Columbia
• Original Assignee: University of British Columbia
• Inventors: Falla, Timothy J., Hancock, Robert E. W., Gough, Monisha
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): Devi, S.
• Application Number:
  US08/702,054
• Time in Patent Office: 1,642 Days
• Field of Search: 530/300, 530/324, 530/326, 530/327, 514/12, 514/13, 424/185.1
• US Class Current: 530/300
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/02 Local antiseptics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: C07K 14/4723 Cationic antimicrobial peptides, e.g. defensins
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A novel class of cationic peptides having antimicrobial activity is disclosed. These peptides can be encompassed by the formulas:

X₁X₁PX₂X₃X₂P(X₂X₂P)_nX₂X₃(X₅)_o; (SEQ ID NO: 23) X₁X₁PX₂X₃X₄(X₅)_rPX₂X₃X₃; (SEQ ID NO: 24) X₁X₁X₃(PW)_uX₃X₂X₅X₂X₂X₅X₂(X₅)_o; and (SEQ ID NO: 25) X₁X₁X₃X₃X₂P(X₂X₂P)_nX₂(X₅)_m; (SEQ ID NO: 26)

wherein:

m is 1 to 5;

n is 1 or 2;

o is 2 to 5;

r is 0 to 8;

u is 0 or 1;

X₁ is Isoleucine, Leucine, Valine, Phenylalanine, Tyrosine, Tryptophan or Methionine;

X₂ represents Tryptophan or Phenylalanine

X₃ represents Arginine or Lysine;

X₄ represents Tryptophan or Lysine; and

X₅ represents Phenylalanine, Tryptophan, Arginine, Lysine, or Proline.

The invention also provides a method of producing a cationic peptide variant having antimicrobial activity.

Claims

1. An isolated cationic peptide selected from the group consisting of:

5. A peptide of claim 1, 2, 3 or 4, wherein the peptide is amidated.

6. A peptide of claim 1, 2, 3 or 4, wherein the peptide is carboxymethylated.

2. An isolated cationic peptide selected from the group consisting of:

3. An isolated cationic peptide consisting of an amino acid sequence selected from the group consisting of:

4. An isolated cationic peptide having an amino acid sequence selected from the group consisting of: