초록 ▼

The invention is directed to peptides having antimicrobial activity (antimicrobial peptides). The antimicrobial peptides of the present invention are analogs of the Lentivirus Lytic Peptide 1 (LLP1) amino acid sequence. The invention is further directed to peptides referred to as the Lytic Base Unit

The invention is directed to peptides having antimicrobial activity (antimicrobial peptides). The antimicrobial peptides of the present invention are analogs of the Lentivirus Lytic Peptide 1 (LLP1) amino acid sequence. The invention is further directed to peptides referred to as the Lytic Base Unit (LBU) peptides derived from the LLP1 analogs, also having antimicrobial activity. In addition, the present invention is also directed to methods of using the peptides in a variety of contexts, including the treatment or prevention of infectious diseases. The antimicrobial LLP1 analog peptides and the LBU peptides (collectively eLLPs) may be highly active under high salt conditions and in biologic fluids. In addition, the eLLPs are effective when presented either in soluble form, or when attached to a solid surface. Furthermore, the peptides of the present invention are selectively active against a wide variety of bacterial pathogens and exhibit minimal toxicity to eukaryotic cells in vitro and in vivo.

대표청구항 ▼

1. An isolated and purified having an amino acid sequence selected from the group consisting of:RVVRVVRRVVRR (SEQ ID NO:4); RRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:5); VRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:6); RRVVRRVRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:7); RVVRVVRRVVRRVRRVVRRVVRVVRR

1. An isolated and purified having an amino acid sequence selected from the group consisting of:RVVRVVRRVVRR (SEQ ID NO:4); RRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:5); VRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:6); RRVVRRVRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:7); RVVRVVRRVVRRVRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRV VRR (SEQ ID NO:8); RVVRVVRRWVRR (SEQ ID NO:9); RRWVRRVRRVWRRVVRVVRRWVRR (SEQ ID NO:10); VRRVWRRVVRVVRRWVRRVRRVWRRVVRVVRRWVRR (SEQ ID NO:11); and RVVRVVRRWVRRVRRVWRRVVRVVRRWVRRVRRVWRRVVRVVRR WRVV (SEQ ID NO:12). 2. The peptide of claim 1 having the amino acid sequence:RVVRVVRRVVRR (SEQ ID NO:4). 3. A composition comprising the peptide of claim 2 and a carrier.4. The peptide of claim 1 having the amino acid sequence:RRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:5). 5. A composition comprising the peptide of claim 4 and a carrier.6. The peptide of claim 1 having the amino acid sequence:VRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:6). 7. A composition comprising the peptide of claim 6 and a carrier.8. The peptide of claim 1 having the amino acid sequence:RRVVRRVRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:7). 9. A composition comprising the peptide of claim 8 and a carrier.10. The peptide of claim 1 having the amino acid sequence:RVVRVVRRVVRRVRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRV VRR (SEQ ID NO:8). 11. A composition comprising the peptide of claim 10 and a carrier.12. The peptide of claim 1 having the amino acid sequence:RVVRVVRRWVRR (SEQ ID NO:9). 13. A composition comprising the peptide of claim 12 and a carrier.14. The peptide of claim 1 having the amino acid sequence:RRWVRRVRRVWRRVVRVVRRWVRR (SEQ ID NO:10). 15. A composition comprising the peptide of claim 14 and a carrier.16. The peptide of claim 1 having the amino acid sequence:VRRVWRRVVRVVRRWVRRVRRVWRRVVRVVRRWVRR (SEQ ID NO:11). 17. A composition comprising the peptide of claim 16 and a carrier.18. The peptide of claim 1 having the amino acid sequence:RVVRVVRRWVRRVRRVWRRVVRVVRRWVRRVRRVWRRVVRVVRR WRVV (SEQ ID NO:12). 19. A composition comprising the peptide of claim 18 and a carrier.20. The peptide of claim 1 wherein said peptide has antimicrobial activity.21. The peptide of claim 1 wherein said peptide has antimicrobial activity in a low salt medium.22. The peptide of claim 1 wherein said peptide has antimicrobial activity in physiological salt.23. An isolated and purified lentiviral lytic peptide-1 peptide analog-comprising an amino acid sequence selected from the group consisting of:RVVRVVRRVVRR (SEQ ID NO:4); RRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:5); VRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:6); RRVVRRVRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:7); RVVRVVRRVVRRVRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRV VRR (SEQ ID NO:8); RVVRVVRRWVRR (SEQ ID NO:9); RRWVRRVRRVWRRVVRVVRRWVRR (SEQ ID NO:10); VRRVWRRVVRVVRRWVRRVRRVWRRVVRVVRRWVRR (SEQ ID NO:11); and RVVRVVRRWVRRVRRVWRRVVRVVRRWVRRVRRVWRRVVRVVRR WRVV (SEQ ID NO:12), and at least one additional residue wherein said peptide analog comprises an amphipathic α-helical structure.24. A solid phase substrate comprising at least one peptide selected from the group consisting of:RVVRVVRRVVRR (SEQ ID NO:4); RRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:5); VRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:6); RRVVRRVRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:7); RVVRVVRRVVRRVRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRV VRR (SEQ ID NO:8); RVVRVVRRWVRR (SEQ ID NO:9); RRWVRRVRRVWRRVVRVVRRWVRR (SEQ ID NO:10); VRRVWRRVVRVVRRWVRRVRRVWRRVVRVVRRWVRR (SEQ ID NO:11); and RVVRVVRRWVRRVRRVWRRVVRVVRRWVRRVRRVWRRVVRVVRR WRVV(SEQ ID NO:12). 25. The solid phase substrate of claim 24 wherein said solid phase substrate is a prosthetic device.26. The solid phase substrate of claim 24 wherein the prosthetic device is a prosthetic joint.27. The peptide of claim 1 wherein said peptide further comprises at least one cysteine residue.28. The peptide of claim 27 wherein said peptide is a disulfide linked dimeric peptide.29. An isolated and purified peptide-cargo complex comprising a cargo and a peptide selected from the group consisting of:RVVRVVRRVVRR (SEQ ID NO:4); RRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO: 5); VRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO: 6); RRVVRRVRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRVVRR (SEQ ID NO:7); RVVRVVRRVVRRVRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRV VRR (SEQ ID NO:8); RVVRVVRRWVRR (SEQ ID NO:9); RRWVRRVRRVWRRVVRVVRRWVRR (SEQ ID NO:10); VRRVWRRVVRVVRRWVRRVRRVWRRVVRVVRRWVRR (SEQ ID NO:11); and RVVRVVRRWVRRVRRVWRRVVRVVRRWVRRVRRVWRRVVRVVRR WRVV (SEQ ID NO:12). 30. The peptide-cargo complex of claim 29 wherein said peptide has antimicrobial activity and said cargo increases the antimicrobial activity of said peptide.