Peptides and methods for inducing cell death
The invention provide isolated peptides, protides and conjugates having novel peptide sequences which are able to induce antimicrobial, anti-cancer, anti-inflammatory, anti-proliferative or programmed cell death activity. The invention also provides a method of inducing programmed cell death in a cell by contacting the cell with an isolated peptide, protide or conjugate described herein. In some aspects, the method can be used in the diagnosis, prevention, or treatment of a disease, such as an infection, cancer, autoimmune disease, or inflammatory disease.
1. An isolated peptide comprising one or more amino acid sequence selected from the group consisting of:
NFNWGRVVALFYFASKLVLKALXTKV (SEQ ID NO: 3), wherein the X amino acid residue at position 23 of SEQ ID NO: 3 is a threonine, a tyrosine, a non-natural H-bond donor residue or a non-natural H-bond acceptor residue;
NFNWGRVVALFYFASKLVLKALXTXV (SEQ ID NO: 4), wherein the X amino acid residue at position 23 of SEQ ID NO: 4 is a lysine, an arginine, an asparagine, a glutamine or a basic residue, and wherein the X amino acid residue at position residue 25 of SEQ ID NO: 4 is a cysteine or a thiol residue;
WGRVVALFYFASKLVLKALXTKV (SEQ ID NO: 6), wherein the X amino acid residue at position 20 of SEQ ID NO: 6 is a threonine, a tyrosine, a non-natural H-bond donor residue or a non-natural H-bond acceptor residue;
RVVALFYFASKLVLKALXTKV (SEQ ID NO: 8), wherein the X amino acid residue at position 18 of SEQ ID NO: 8 is a threonine, a tyrosine, a non-natural H-bond donor residue or a non-natural H-bond acceptor residue;
ALFYFASKLVLKALXTKV (SEQ ID NO: 10), wherein the X amino acid residue at position 15 of SEQ ID NO: 10 is a threonine, a tyrosine, a non-natural H-bond donor residue or a non-natural H-bond acceptor residue;
TWQTVTIFVAXVLTASLTIWKK (SEQ ID NO: 11), wherein the X amino acid residue at position 11 of SEQ ID NO: 11 is a lysine, an arginine, an asparagine, a glutamine or a basic residue; and
TVTIFVAXVLTASLTIWKK (SEQ ID NO: 13), wherein the X amino acid residue at position 8 of SEQ ID NO: 13 is a lysine, an arginine, an asparagine, a glutamine or a basic residue,
and wherein said peptide induces antimicrobial, anti-cancer, anti-inflammatory, anti-proliferative or programmed cell death activity.
2. The isolated peptide of claim 1 , wherein said peptide comprises the amino acid sequence NFNWGRVVALFYFASKLVLKALXTKV (SEQ ID NO: 3), wherein the X amino acid residue at position 23 of SEQ ID NO: 3 is a threonine, a tyrosine, a non-natural H-bond donor residue or a non-natural H-bond acceptor residue.
3. An isolated peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 5, 7, 9 and 12, wherein said peptide induces antimicrobial, anti-cancer, anti-inflammatory, anti-proliferative or programmed cell death activity.
4. The isolated peptide of claim 2 , wherein said peptide consists of the amino acid sequence of NFNWGRVVALFYFASKLVLKALYTKV (SEQ ID NO: 270).
5. The isolated peptide of claim 1 , wherein said peptide comprises the amino acid sequence of NFNWGRVVALFYFASKLVLKALXTXV (SEQ ID NO: 4), wherein the X amino acid residue at position 23 of SEQ ID NO: 4 is a lysine, an arginine, an asparagine, a glutamine or a basic residue, and wherein the X amino acid residue at position 25 of SEQ ID NO: 4 is a cysteine or a thiol residue.
6. The isolated peptide of claim 1 , wherein said peptide comprises the amino acid sequence of WGRVVALFYFASKLVLKALXTKV (SEQ ID NO: 6), wherein the X amino acid residue at position 20 of SEQ ID NO: 6 is a threonine, a tyrosine, a non-natural H-bond donor residue or a non-natural H-bond acceptor residue.
7. The isolated peptide of claim 1 , wherein said peptide comprises the amino acid sequence of RVVALFYFASKLVLKALXTKV (SEQ ID NO: 8), wherein the X amino acid residue at position 18 of SEQ ID NO: 8 is a threonine, a tyrosine, a non-natural H-bond donor residue or a non-natural H-bond acceptor residue.
8. The isolated peptide of claim 1 , wherein said peptide comprises the amino acid sequence of ALFYFASKLVLKALXTKV (SEQ ID NO: 10), wherein the X amino acid residue at position 15 of SEQ ID NO: 10 is a threonine, a tyrosine, a non-natural H-bond donor residue or a non-natural H-bond acceptor residue.
9. The isolated peptide of claim 8 , wherein said peptide consists of the amino acid sequence of ALFYFASKLVLKALYTKV (SEQ ID NO: 264).
10. The isolated peptide of claim 1 , wherein said peptide comprises the amino acid sequence of TWQTVTIFVAXVLTASLTIWKK (SEQ ID NO: 11), wherein the X amino acid residue at position 11 of SEQ ID NO: 11 is a lysine, an arginine, an asparagine, a glutamine or a basic residue.
11. The isolated peptide of claim 1 , wherein said peptide comprises the amino acid sequence of TVTIFVAXVLTASLTIWKK (SEQ ID NO: 13), wherein the X amino acid residue at position 8 of SEQ ID NO: 13 is a lysine, an arginine, an asparagine, a glutamine or a basic residue.
12. The isolated peptide of claim 11 , wherein said peptide consists of the amino acid sequence of TVTIFVAKVLTASLTIWKK (SEQ ID NO: 271).
13. The isolated peptide of claim 3 , wherein said peptide consists of the amino acid sequence of SEQ ID NO: 1.
14. The isolated peptide of claim 3 , wherein said peptide consists of the amino acid sequence of SEQ ID NO: 5.
15. The isolated peptide of claim 3 , wherein said peptide consists of the amino acid sequence of SEQ ID NO: 7.
16. The isolated peptide of claim 3 , wherein said peptide consists of the amino acid sequence of SEQ ID NO: 9.
17. The isolated peptide of claim 3 , wherein said peptide consists of the amino acid sequence of SEQ ID NO: 12.
18. An isolated peptide consisting of the amino acid sequence selected from the group consisting of:
NFNWGRVVALFYFASKLVLKALXTKV (SEQ ID NO: 3), wherein the X amino acid residue at position 23 of SEQ ID NO: 3 is a serine;
WGRVVALFYFASKLVLKALXTKV (SEQ ID NO: 6), wherein the X amino acid residue at position 20 of SEQ ID NO: 6 is a serine;
RVVALFYFASKLVLKALXTKV (SEQ ID NO: 8), wherein the X amino acid residue at position 18 of SEQ ID NO: 8 is a serine; and
ALFYFASKLVLKALXTKV (SEQ ID NO: 10), wherein the X amino acid residue at position 15 of SEQ ID NO: 10 is a serine,
and wherein said peptide induces antimicrobial, anti-cancer, anti-inflammatory, anti-proliferative or programmed cell death activity.
19. The isolated peptide of claim 18 , wherein the peptide consists of the amino acid sequence of NFNWGRVVALFYFASKLVLKALXTKV (SEQ ID NO: 3), wherein the X amino acid residue at position 23 of SEQ ID NO: 3 is a serine.
20. The isolated peptide of claim 18 , wherein the peptide consists of the amino acid sequence of WGRVVALFYFASKLVLKALXTKV (SEQ ID NO: 6), wherein the X amino acid residue at position 20 of SEQ ID NO: 6 is a serine.
21. The isolated peptide of claim 18 , wherein the peptide consists of the amino acid sequence of RVVALFYFASKLVLKALXTKV (SEQ ID NO: 8), wherein the X amino acid residue at position 18 of SEQ ID NO: 8 is a serine.
22. The isolated peptide of claim 18 , wherein the peptide consists of the amino acid sequence of ALFYFASKLVLKALXTKV (SEQ ID NO: 10), wherein the X amino acid residue at position 15 of SEQ ID NO: 10 is a serine.
23. A method of inducing programmed cell death in a cell, comprising contacting said cell with the isolated peptide of any one of claims 1 , 2 , 3 and 4 - 22 .