Therapeutic TREM-1 peptides
A polypeptide comprising one or more sequences derived from CDR2 or CDR3 of a TREM-1 protein, characterised by the ability to treat, ameliorate, or lessen the symptoms of conditions including sepsis, septic shock or sepsis-like conditions and IBD.
1. An isolated polynucleotide comprising a nucleotide sequence, which encodes a peptide which is capable of acting as antagonist of the TREM-1 protein as defined by SEQ ID NO: 2 and one or more expression control elements that control expression of the peptide;
wherein the peptide comprises SEQ ID NO: 22 or at least 3 amino acids from SEQ ID NO: 23; and
wherein the peptide consists of:
(i) a contiguous sequence of 5 to 29 amino acids from SEQ ID NO: 2; or
(ii) a contiguous sequence of 5 to 29 amino acids from SEQ ID NO: 2 in which one amino acid is substituted conservatively with another amino acid.
2. A vector comprising the polynucleotide of claim 1 .
3. An isolated polynucleotide comprising a nucleotide sequence, which encodes a peptide consisting of SEQ ID NO: 19 or SEQ ID NO: 7 and a heterologous signal sequence.
4. A vector comprising the isolated polynucleotide of claim 2 .
5. An isolated polynucleotide comprising a nucleotide sequence encoding a peptide and one or more expression control elements that control expression of the peptide; wherein the peptide is capable of acting as an antagonist of the TREM-1 protein as defined by SEQ ID NO: 1;
wherein the peptide comprises the amino acid sequence of SEQ ID NO: 20 or at least 3 amino acids of SEQ ID NO: 21; and
wherein the peptide consists of:
(i) a contiguous sequence of 5 to 29 amino acids from SEQ ID NO: 1; or
(ii) a contiguous sequence of 5 to 29 amino acids from SEQ ID NO: 1 in which one amino acid is substituted conservatively with another amino acid.
6. A vector comprising the polynucleotide of claim 5 .
7. The polynucleotide of claim 5 , wherein the peptide consists of an amino acid sequence having the sequence of SEQ ID NOs: 16, 17, 18 or 19.
8. The polynucleotide of claim 7 , wherein the peptide consists of an amino acid sequence having the sequence of SEQ ID NO: 19.
9. The polynucleotide of claim 5 , wherein the peptide consists of an amino acid sequence having the sequence of SEQ ID NOs: 16, 17, 18 or 19, or which differs from the sequence of SEQ ID NO: 16, 17, 18, or 19 by one or more conservative amino acid modifications.
10. The polynucleotide of claim 9 , wherein the peptide consists of an amino acid sequence having the sequence of SEQ ID NO: 19, or which differs from the sequence of SEQ ID NO: 19 by one or more conservative amino acid modifications.
11. The polynucleotide of claim 5 , wherein the peptide consists of a contiguous sequence of 5 to 29 amino acids from SEQ ID NO: 1.
12. The polynucleotide of claim 5 , wherein the peptide comprises at least 3 amino acids from SEQ ID NO: 21, wherein the at least 3 amino acids from SEQ ID NO: 21 are selected from the group consisting of QPP, QPPK (SEQ ID NO: 24), and QPPKE (SEQ ID NO: 21).
13. The vector of claim 6 , wherein the expression control element comprises a promoter, an enhancer, a transcription terminator, or a polyadenylation site.
14. A host cell comprising the polynucleotide of claim 5 .
15. The host cell of claim 14 , which is a prokaryotic cell.
16. The host cell of claim 14 , which is a eukaryotic cell.
17. A method of expressing a peptide in a host cell comprising transforming the host cell with the polynucleotide of claim 5 in a culture medium.
18. The method of claim 17 , further comprising purifying the expressed peptide.