Human cathelicidin antimicrobial peptides
View Patent ↗Provided are peptide and peptide consensus sequences, which inhibit bacterial growth and/or viral growth and mimic the activity of LL-37, CRAMP, and/or FALL-39. The peptides are useful as antimicrobials, anti-inflammatories and anti-viral agents.
1. A method for inhibiting the spread and/or reducing the risk of infection of a virus comprising contacting a virus with an inhibiting effective amount of a cathelicidin functional fragment, wherein the cathelicidin functional fragment consists of 16-20 or 26-30 amino acids in length; and contains the sequence X 1 X 2 X 3 X 4 X 5 X 6 IKX 7 FX 8 X 9 X 10 LX 11 P (SEQ ID NO:1), wherein X 1 , X 2 , and X 6 are individually K or R; wherein X 3 is I or K; wherein X 4 is V or G; wherein X 5 is Q or R; wherein X 7 , X 9 , X 10 , and X 11 are each individually any amino acid; wherein X 8 is L or F and wherein the polypeptide comprises antimicrobial and/or antiviral activity.
2. The method of claim 1 , wherein the peptide comprises a sequence selected from the group consisting of:
(a)
KRIVQRIKDFLRNLVP;
(SEQ ID NO:13)
(b)
KRIVQRIKDFLRNLVPR;
(SEQ ID NO:14)
(c)
KRIVQRIKDFLRNLVPRT;
(SEQ ID NO:15)
(d)
KRIVQRIKDFLRNLVPRTE;
(SEQ ID NO:16)
and
(e)
KRIVQRIKDFLRNLVPRTES.
(SEQ ID NO:17)
3. The method of claim 1 , wherein the peptide comprises a sequence selected from the group consisting of:
(a)
KSKEKIGKEFKRIVQRIKDFLRNLVP;
(SEQ ID NO:18)
(b)
KSKEKIGKEFKRIVQRIKDFLRNLVPR;
(SEQ ID NO:19)
(c)
KSKEKIGKEFKRIVQRIKDFLRNLVPRT;
(SEQ ID NO:20)
(d)
KSKEKIGKEFKRIVQRIKDFLRNLVPRTE;
(SEQ ID NO:21)
and
(e)
KSKEKIGKEFKRIVQRIKDFLRNLVPRTES.
(SEQ ID NO:22)
4. A method for inhibiting the spread and/or reducing the risk of infection of a virus comprising contacting a virus with an inhibiting effective amount of a cathelicidin functional fragment, wherein the fragment consists of a sequence selected form the group consisting of:
(a)
RKSKEKIGKEFKRIVQRIKDFLRNLVP;
(SEQ ID NO:23)
(b)
RKSKEKIGKEFKRIVQRIKDFLRNLVPR;
(SEQ ID NO:24)
(c)
RKSKEKIGKEFKRIVQRIKDFLRNLVPRT;
(SEQ ID NO:25)
(d)
RKSKEKIGKEFKRIVQRIKDFLRNLVPRTE;
(SEQ ID NO:26)
(e)
RKSKEKIGKEFKRIVQRIKDFLRNLVPRTES.
(SEQ ID NO:27)
(f)
LGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES.
(SEQ ID NO: 28)
5. The method of claim 1 , wherein the virus is selected from a pox virus, a herpes virus, vaccinia virus, and pappiloma virus.
6. The method of claim 1 , wherein the contacting is in vivo.
7. The method of claim 6 , wherein the contacting is in vivo is by topical administration.
8. A method for treating atopic dermatitis comprising contacting a subject having or suspected of having atopic dermatitis with an inhibiting effective amount of a cathelicidin functional fragment, wherein the cathelicidin functional fragment consists of 16-20or 26-30 amino acids in length; and contains the sequence X 1 X 2 X 3 X 4 X 5 X 6 IKX 7 FX 8 X 9 X 10 LX 11 P (SEQ ID NO: 1), wherein X 1 , X 2 , and X 6 are individually K or R; wherein X 3 is I or K; wherein X 4 is V or G; wherein X 5 is Q or R; wherein X 7 , X 9 , X 10 , and X 11 are each individually any amino acid; wherein X 8 is L or F and wherein the polypeptide comprises antimicrobial and/or antiviral activity.
9. The method of claim 8 , wherein the peptide comprises a sequence selected from the group consisting of:
(a)
KRIVQRIKDFLRNLVP;
(SEQ ID NO:13)
(b)
KRIVQRIKDFLRNLVPR;
(SEQ ID NO:14)
(c)
KRIVQRIKDFLRNLVPRT;
(SEQ ID NO:15)
(d)
KRIVQRIKDFLRNLVPRTE;
(SEQ ID NO:16)
and
(e)
KRIVQRIKDFLRNLVPRTES.
(SEQ ID NO:17)
10. The method of claim 8 , wherein the peptide comprises a sequence selected from the group consisting of:
(a)
KSKEKIGKEFKRIVQRIKDFLRNLVP;
(SEQ ID NO:18)
(b)
KSKEKIGKEFKRIVQRIKDFLRNLVPR;
(SEQ ID NO:19)
(c)
KSKEKIGKEFKRIVQRIKDFLRNLVPRT;
(SEQ ID NO:20)
(d)
KSKEKIGKEFKRIVQRIKDFLRNLVPRTE;
(SEQ ID NO:21)
and
(e)
KSKEKIGKEFKRIVQRIKDFLRNLVPRTES.
(SEQ ID NO:22)
11. A method for treating atopic dermatitis comprising contacting a subject having or suspected of having atopic dermatitis with an inhibiting effective amount of a cathelicidin functional fragment, wherein the fragment consists of a sequence selected from the group consisting of:
(a)
RKSKEKIGKEFKRIVQRIKDFLRNLVP;
(SEQ ID NO:23)
(b)
RKSKEKIGKEFKRIVQRIKDFLRNLVPR;
(SEQ ID NO:24)
(c)
RKSKEKIGKEFKRIVQRIKDFLRNLVPRT;
(SEQ ID NO:25)
(d)
RKSKEKIGKEFKRIVQRIKDFLRNLVPRTE;
(SEQ ID NO:26)
(e)
RKSKEKIGKEFKRIVQRIKDFLRNLVPRTES.
(SEQ ID NO:27)
(f)
LGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES.
(SEQ ID NO: 28)
12. The method of claim 8 or 11 , wherein the subject also is inflected with a viral infection, wherein the virus is selected from a pox virus, a herpes virus, vaccinia virus, and pappiloma virus.
13. The method of claim 8 or 11 , wherein the contacting is in vivo.
14. The method of claim 13 , wherein the contacting in vivo is by topical administration.