Therapeutic trem-1 peptides

Abstract

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 peptide or a derivative thereof, which is capable of acting as antagonist of the TREM-1 protein as defined by SEQ ID NO.2, comprising SEQ ID NO. 22 or at least 3 amino acids from SEQ ID NO. 23, wherein:
 (a) the polypeptide 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; or 
   (b) the polypeptide consists of an amino acid sequence having at least 80% sequence identity to SEQ ID NOS: 3, 4, 6 or 7;   wherein the derivatives of the polypeptides of (a) or (b) are modified by glycosylation, acetylation, pegylation, phosphorylation, amidation, or derivatization by protecting or blocking groups.   
     
     
         2 . An isolated polynucleotide encoding the peptide or derivative thereof of  claim 1 . 
     
     
         3 . A vector comprising the polynucleotide of  claim 2 . 
     
     
         4 . A method of treating sepsis, septic shock, or an inflammatory disorder in a subject in need thereof comprising administering to the subject the peptide or derivative thereof of  claim 1 . 
     
     
         5 . An isolated polypeptide consisting of SEQ ID NO: 19 or SEQ ID NO: 7. 
     
     
         6 . An isolated polynucleotide encoding the polypeptide of  claim 5 . 
     
     
         7 . A vector comprising the polynucleotide of  claim 6 . 
     
     
         8 . A method of treating sepsis, septic shock, or an inflammatory disorder in a subject in need thereof comprising administering to the subject the polypeptide of  claim 5 . 
     
     
         9 . An isolated peptide or derivative thereof, which is capable of acting as an antagonist of the TREM-1 protein as defined by SEQ ID NO. 1, comprising the amino acid sequence of SEQ ID NO. 20 or at least 3 amino acids of SEQ ID NO. 21, wherein:
 (a) 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; or 
   (b) the peptide consists of an amino acid sequence having at least 80% sequence identity to SEQ ID NOs: 16, 17, 18 or 19; and   wherein the derivatives of the peptides of (a) or (b) are modified by glycosylation, acetylation, pegylation, phosphorylation, amidation, or derivatization by protecting or blocking groups.   
     
     
         10 . An isolated polynucleotide encoding the peptide or derivative thereof of  claim 9 . 
     
     
         11 . A vector comprising the polynucleotide of  claim 10 . 
     
     
         12 . A method of treating sepsis, septic shock, or an inflammatory disorder in a subject in need thereof comprising administering to the subject the peptide or derivative thereof of  claim 9 . 
     
     
         13 . The method of  claim 12 , wherein the disorder comprises inflammatory bowel disease (IBD). 
     
     
         14 . The method of  claim 12 , wherein the peptide or derivative thereof consists of:
 (a) a contiguous sequence of 5 to 29 amino acids from SEQ ID NO: 1; or   (b) 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; and   wherein the derivatives of the peptides of (a) or (b) are modified by glycosylation, acetylation, pegylation, phosphorylation, amidation, or derivatization by protecting or blocking groups.   
     
     
         15 . The method of  claim 12 , wherein the peptide or derivative thereof consists of an amino acid sequence having at least 80% sequence identity to SEQ ID NOs: 16, 17, 18 or 19;
 and wherein the derivatives of the peptide are modified by glycosylation, acetylation, pegylation, phosphorylation, amidation, or derivatization by protecting or blocking groups.   
     
     
         16 . The method of  claim 15 , wherein the peptide consists of an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 19. 
     
     
         17 . The method of  claim 15 , 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 said sequence by one or more conservative amino acid modifications. 
     
     
         18 . The method of  claim 17 , wherein the peptide consists of an amino acid having the sequence of SEQ ID NO: 19, or which differs from said sequence by one or more conservative modifications. 
     
     
         19 . The method of  claim 12 , wherein the peptide consists of a contiguous sequence of 5 to 29 amino acids from SEQ ID NO. 1. 
     
     
         20 . The method of  claim 12 , wherein the peptide or derivative 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).