IP Library › Granted Patent US 7,713,927

Granted Patent B2

US 7,713,927 · App. 12/014,634 · Granted May 11, 2010

Antimicrobial peptides

Assignees: The Regents of the University of California; C3 Jian, Inc.

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Quick Facts

Patent No.: US 7,713,927
App. No.: 12/014,634
Granted: May 11, 2010
Kind: B2

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Abstract

This invention provides novel antimicrobial peptides that are effective to inhibit growth and/or proliferation of various gram positive bacteria. In particular, the peptides are effective against Streptococcus mutans a common oral pathogen and the causative agent of dental caries.

Claims (57)

1. An antimicrobial peptide comprising an amino acid sequence selected from the group consisting of KLFKRWKHLFR (SEQ ID NO:33) (B-35), RLLKRFKHLFK (SEQ ID NO:34) (B-36), FKTFLKWLHRF (SEQ ID NO:35) (B-37), IKQLLHFFQRF (SEQ ID NO:36) (B-38), KLLQTFKQIFR (SEQ ID NO:37) (B-39), RILKELKNLFK (SEQ ID NO:38) (B-40), LKQFVHFIHRF (SEQ ID NO:39) (B-41), VKTLLHIFQRF (SEQ ID NO:40) (B-42), KLVEQLKEIFR (SEQ ID NO:41) (B-43), RVLQEIKQILK (SEQ ID NO:42) (B-44), VKNLAELVHRF (SEQ ID NO:43) (B-45), ATHLLHALQRF (SEQ ID NO:44) (B-46), KLAENVKEILR (SEQ ID NO:45) (B-47), RALHEAKEALK (SEQ ID NO:46) (B-48), FHYFWHWFHRF (SEQ ID NO:47) (B-49), LYHFLHWFQRF (SEQ ID NO:48) (B-50), YLFQTWQHLFR (SEQ ID NO:49) (B-51), YLLTEFQHLFK (SEQ ID NO:50) (B-52), FKTFLQWLHRF (SEQ ID NO:51) (B-53), IKTLLHFFQRF (SEQ ID NO:52) (B-54), KLLQTFNQIFR (SEQ ID NO:53) (B-55), TILQSLKNIFK (SEQ ID NO:54) (B-56), LKQFVKFIHRF (SEQ ID NO:55) (B-57), VKQLLKIFNRF (SEQ ID NO:56) (B-58), KLVQQLKNIFR (SEQ ID NO:57) (B-59), RVLNQVKQILK (SEQ ID NO:58) (B-60), VKKLAKLVRRF (SEQ ID NO:59) (B-61), AKRLLKVLKRF (SEQ ID NO:60) (B-62), KLAQKVKRVLR (SEQ ID NO:61) (B-63), and RALKRIKHVLK (SEQ ID NO:62) (B-64).

2. An antimmicrobial peptide comprising an amino acid sequence selected from the group consisting of, LKLLKKLLKLLKKF (SEQ ID NO:65) (α-6), LQLLKQLLKLLKQF (SEQ ID NO:66) (α-7), RWRRWWRHFHHFFH (SEQ ID NO:68) (α-9), KLKKLLKRWRRWWR (SEQ ID NO:69) (α-10), RWRRLLKKLHHLLH (SEQ ID NO:70) (α-11), and KLKKLLKHLHHLLH (SEQ ID NO:71) (α-12).

3. The antimicrobial peptide of any one of claims 1 and 2 , wherein said peptide further comprises a free amine at the carboxyl terminus.

4. The antimicrobial peptide of claim 3 , wherein said peptide comprises a free amine at the carboxyl terminus that is provided by arginine or lysine.

5. The antimicrobial peptide of claim 3 , wherein said peptide comprises a free amine at the carboxyl terminus that is provided by an amidated non-cationic residue.

6. The antimicrobial peptide of any one of claims 1 and 2 , wherein said peptide is pegylated.

7. The antimicrobial peptide of any one of claims 1 and 2 , wherein said peptide bears one or more protecting groups.

8. The antimicrobial peptide of any one of claims 1 and 2 , wherein said peptide bears one or more protecting groups selected from the group consisting of acetyl, amide, and 3 to 20 carbon alkyl groups, Fmoc, Tboc, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-florenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl, Xanthyl (Xan), Trityl (Trt), 4-methyltrityl (Mtt), 4-methoxytrityl (Mmt), 4-methoxy-2,3,6-trimethyl-benzenesulphonyl (Mtr), Mesitylene-2-sulphonyl (Mts), 4,4-dimethoxybenzhydryl (Mbh), Tosyl (Tos), 2,2,5,7,8-pentamethyl chroman-6-sulphonyl (Pmc), 4-methylbenzyl (MeBzl), 4-methoxybenzyl (MeOBzl), Benzyloxy (BzlO), Benzyl (Bzl), Benzoyl (Bz), 3-nitro-2-pyridinesulphenyl (Npys), 1-(4,4-dimentyl-2,6-diaxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl (2,6-DiCl-Bzl), 2-chlorobenzyloxycarbonyl (2-Cl-Z), 2-bromobenzyloxycarbonyl (2-Br-Z), Benzyloxymethyl (Born), t-butoxycarbonyl (Boc), cyclohexyloxy (cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), Acetyl (Ac), and Trifluoroacetyl (TFA).

9. The antimicrobial peptide of claim 1 , wherein said peptide is amidated.

10. The antimicrobial peptide of claim 2 , wherein said peptide is amidated.

11. The antimicrobial peptide of any one of claims 1 and 2 , wherein said peptide is labeled with a detectable label.

12. The antimicrobial peptide of claim 11 , wherein said peptide is labeled with a detectable label selected from the group consisting of an enzymatic label, a fluorescent label, a colorimetric label, a spin label, and a radioactive label.

13. The antimicrobial peptide of any one of claims 1 and 2 , wherein said peptide is attached to a second antimicrobial peptide thereby forming a compound antimicrobial peptide.

14. The antimicrobial peptide of claim 13 , wherein said compound antimicrobial peptide is a fusion protein.

15. The antimicrobial peptide of claim 14 , wherein said second antimicrobial peptide is selected from the group consisting of SEQ ID NOs: 31-87.

16. A pharmaceutical formulation comprising an antimicrobial peptide of any one of claim 1 or 2 ; and

a pharmaceutically acceptable excipient.

17. The pharmaceutical formulation of claim 16 , wherein said formulation is a unit dosage formulation.

18. The pharmaceutical formulation of claim 16 , wherein said excipient is acceptable for administration to an oral mucosa.

19. A health care product comprising an antimicrobial peptide according to any of claims 1 and 2 , wherein said antimicrobial peptide is contained in a product selected from the group consisting of toothpaste, mouthwash, a tooth whitening strip or solution, s contact lens storage, wetting, or cleaning solution, dental floss, a toothpick, a toothbrush bristle, an oral spray, an oral lozenge, a nasal spray, an aerosolizer for oral and/or nasal application, and a wound dressing.

20. The antimicrobial peptide according to any of claim 1 or 2 , wherein the amino acid sequence of said peptide consists of a sequence selected from the group consisting of KLFKRWKHLFR (SEQ ID NO:33) (B-35), RLLKRFKHLFK (SEQ ID NO:34) (B-36), FKTFLKWLHRF (SEQ ID NO:35) (B-37), IKQLLHFFQRF (SEQ ID NO:36) (B-38), KLLQTFKQIFR (SEQ ID NO:37) (B-39), RILKELKNLFK (SEQ ID NO:38) (B-40), LKQFVHFIHRF (SEQ ID NO:39) (B-41), VKTLLHIFQRF (SEQ ID NO:40) (B-42), KLVEQLKEIFR (SEQ ID NO:41) (B-43), RVLQEIKQILK (SEQ ID NO:42) (B-44), VKNLAELVHRF (SEQ ID NO:43) (B-45), ATHLLHALQRF (SEQ ID NO:44) (B-46), KLAENVKEILR (SEQ ID NO:45) (B-47), RALHEAKEALK (SEQ ID NO:46) (B-48), FHYFWHWFHRF (SEQ ID NO:47) (B-49), LYHFLHWFQRF (SEQ ID NO:48) (B-50), YLFQTWQHLFR (SEQ ID NO:49) (B-51), YLLTEFQHLFK (SEQ ID NO:50) (B-52), FKTFLQWLHRF (SEQ ID NO:51) (B-53), IKTLLHFFQRF (SEQ ID NO:52) (B-54), KLLQTFNQIFR (SEQ ID NO:53) (B-55), TILQSLKNIFK (SEQ ID NO:54) (B-56), LKQFVKFIHRF (SEQ ID NO:55) (B-57), VKQLLKIFNRF (SEQ ID NO:56) (B-58), KLVQQLKNIFR (SEQ ID NO:57) (B-59), RVLNQVKQILK (SEQ ID NO:58) (B-60), VKKLAKLVRRF (SEQ ID NO:59) (B-61), AKRLLKVLKRF (SEQ ID NO:60) (B-62), KLAQKVKRVLR (SEQ ID NO:61) (B-63), RALKRIKHVLK (SEQ ID NO:62) (B-64), LKLLKKLLKLLKKF (SEQ ID NO:65) (α-6), LQLLKQLLKLLKQF (SEQ ID NO:66) (α-7), RWRRWWRHFHHFFH (SEQ ID NO:68) (α-9), KLKKLLKRWRRWWR (SEQ ID NO:69) (α-10), RWRRLLKKLHHLLH (SEQ ID NO:70) (α-11), and KLKKLLKHLHHLLH (SEQ ID NO:71) (α-12).

21. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence KLFKRWKHLFR (SEQ ID NO:33).

22. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence RLLKRFKHLFK (SEQ ID NO:34).

23. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence FKTFLKWLHRF (SEQ ID NO:35).

24. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence IKQLLHFFQRF (SEQ ID NO:36).

25. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence KLLQTFKQIFR (SEQ ID NO:37).

26. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence RILKELKNLFK (SEQ ID NO:38).

27. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence LKQFVHFIHRF (SEQ ID NO:39).

28. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence VKTLLHIFQRF (SEQ ID NO:40).

29. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence KLVEQLKEIFR (SEQ ID NO:41).

30. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence RVLQEIKQILK (SEQ ID NO:42).

31. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence VKNLAELVHRF (SEQ ID NO:43).

32. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence ATHLLHALQRF (SEQ ID NO:44).

33. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence KLAENVKEILR (SEQ ID NO:45).

34. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence RALHEAKEALK (SEQ ID NO:46).

35. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence FHYFWHWFHRF (SEQ ID NO:47).

36. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence LYHFLHWFQRF (SEQ ID NO:48).

37. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence YLFQTWQHLFR (SEQ ID NO:49).

38. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence YLLTEFQHLFK (SEQ ID NO:50).

39. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence FKTFLQWLHRF (SEQ ID NO:51).

40. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence IKTLLHFFQRF (SEQ ID NO:52).

41. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence KLLQTFNQIFR (SEQ ID NO:53).

42. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence TILQSLKNIFK (SEQ ID NO:54).

43. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence LKQFVKFIHRF (SEQ ID NO:55).

44. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence VKQLLKIFNRF (SEQ ID NO:56).

45. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence KLVQQLKNIFR (SEQ ID NO:57).

46. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence RVLNQVKQILK (SEQ ID NO:58).

47. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence VKKLAKLVRRF (SEQ ID NO:59).

48. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence AKRLLKVLKRF (SEQ ID NO:60).

49. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence KLAQKVKRVLR (SEQ ID NO:61).

50. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence RALKRIKHVLK (SEQ ID NO:62).

51. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence LKLLKKLLKLLKKF (SEQ ID NO:65).

52. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence LQLLKQLLKLLKQF (SEQ ID NO:66).

53. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence RWRRWWRHFHHFFH (SEQ ID NO:68).

54. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence KLKKLLKRWRRWWR (SEQ ID NO:69).

55. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence RWRRLLKKLHHLLH (SEQ ID NO:70).

56. The antimicrobial peptide according to claim 1 wherein the amino acid sequence of said peptide comprises the sequence KLKKLLKHLHHLLH (SEQ ID NO:71).

Assignments (4)

SECURITY INTEREST Recorded May 20, 2026

From: ARMATA PHARMACEUTICALS, INC.; C3J THERAPEUTICS, INC; C3 JIAN, LLC

To: INNOVIVA STRATEGIC OPPORTUNITIES LLC

Reel/Frame 074715/0208 →

EXECUTIVE ORDER 9424, CONFIRMATORY LICENSE Recorded Mar 10, 2009

From: UNIVERSITY OF CALIFORNIA LOS ANGELES

To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT

Reel/Frame 022370/0629 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 27, 2008

From: ANDERSON, MAXWELL H.

To: C3 JIAN, INC.