Platelet promoting protein and the usage thereof

Abstract

The present invention discloses a protein that has strong affinity to thrombopoietin receptor (C-MPL) and the nucleotide sequences of the protein. The protein is capable of increasing the numbers of platelets and enhancing the blood clotting in vivo and is named as platelet promoting protein (PPP). The protein and its nucleotide sequences can be used for the treatment of blood diseases including thrombocytopenia.

1 . An isolated human-derived protein, having an amino acid sequence of:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   MGGEQEEERF DGMLLAMAQQ HEGGVQELVN TFFSFLRRKT 
                     
                 
                     
                     
                 
                     
                   DFFIGGEEGM AEKLITQTFS HHNQLAQKTR REKRARQEAE 
                 
                     
                     
                 
                     
                   RREKAERAAR LAKEAKSETS GPQIKELTDE EAERLQLEID 
                 
                     
                     
                 
                     
                   QKKDAENHEA QLKNGSLDSP GKQDTEEDEE EDEKDKGKLK 
                 
                     
                     
                 
                     
                   PNLGNGADLP NYRWTQTLSE LDLAVPFCVN FRLKGKDMVV 
                 
                     
                     
                 
                     
                   DIQRRHLRVG LKGQPAIIDG ELYNEVKVEE SSWLIEDGKV 
                 
                     
                     
                 
                     
                   VTVHLEKINK MEWWSRLVSS DPEINTKKIN PENSKLSDLD 
                 
                     
                     
                 
                     
                   SETRSMVEKM MYDQRQKSMG LPTSDEQKKQ EILKKFMDQH 
                 
                     
                     
                 
                     
                   PEMDFSKAKF N; 
                 
                     
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         or a derivative thereof with a function of increasing the numbers of blood platelets.  
       
     
     
         2 . The isolated protein according to  claim 1 , wherein the protein has additional 2-6 histidines at the N-terminus of the protein.  
     
     
         3 . The isolated protein according to  claim 1  wherein the amino acid sequence of protein is encoded by the nucleotide sequence of:  
       
         
           
                 
                 
               
                     
                 
                   atgggcggagagcaggaggaggagcggttcgacggcatgttgctggccat 
                     
                 
                     
                 
                   ggctcagcagcacgagggcggcgtgcaggagcttgtgaacaccttcttca 
                 
                     
                 
                   gcttccttcgacgcaaaacagactttttcattggaggagaagaagggatg 
                 
                     
                 
                   gcagagaagcttatcacacagactttcagccaccacaatcagctggcaca 
                 
                     
                 
                   gaagacccggcgggagaagagagcccggcaggaggccgagcggcgggaga 
                 
                     
                 
                   aggcggagcgggcggccagactggccaaggaagccaagtcagagacctca 
                 
                     
                 
                   gggccccagatcaaggagctaactgatgaagaggcagagaggctgcagct 
                 
                     
                 
                   agagattgaccagaaaaaggatgcagagaatcatgaggcccagctcaaga 
                 
                     
                 
                   acggcagccttgactccccagggaagcaggatactgaggaagatgaggag 
                 
                     
                 
                   gaagatgagaaggacaaaggaaaactgaagcccaacctaggcaacggggc 
                 
                     
                 
                   agacctgcccaattaccgctggacccagaccctgtcggagctggacctgg 
                 
                     
                 
                   cggtccctttctgtgtgaacttccggctgaaagggaaggacatggtggtg 
                 
                     
                 
                   gacatccagcggcggcacctccgggtggggctcaaggggcagccagcgat 
                 
                     
                 
                   cattgatggggagctctacaatgaagtgaaggtggaggagagctcgtggc 
                 
                     
                 
                   tcattgaggacggcaaggtggtgactgtgcatctggagaagatcaataag 
                 
                     
                 
                   atggagtggtggagccgcttggtgtccagtgaccctgagatcaacaccaa 
                 
                     
                 
                   gaagattaaccctgagaattccaagctgtcagacctggacagtgagactc 
                 
                     
                 
                   gcagcatggtggaaaagatgatgtatgaccagcgacagaagtccatgggg 
                 
                     
                 
                   ctgccaacttcagacgaacagaagaaacaggagattctgaagaagttcat 
                 
                     
                 
                   ggatcaacatccggagatggatttttccaaggctaaattcaac. 
                 
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         4 . A plasmid, comprising a nucleotide sequence for encoding the amino acid sequence of the protein according to  claim 1 .  
     
     
         5 . The plasmid according to  claim 4 , wherein the plasmid is the expression vector PET-PPP.  
     
     
         6 . A method of making a pharmaceutical composition comprising incorporating a protein according to  claim 1  in medicament for treatment of thrombocytopenia or hemorrhage.  
     
     
         7 . The method according to  claim 6 , wherein the medicament is in a form of injections, powders, tablets, capsules, solutions, suspensions, or emulsions.  
     
     
         8 . The method according to  claim 6 , wherein the medicament is in a form for oral administration or in a form administration via subcutaneous injection, intravenous injection or intramuscular injection.  
     
     
         9 . A pharmaceutical composition, comprising the protein according to  claim 1  or a derivative thereof with a function of increasing the numbers of platelets, and at least one pharmaceutically acceptable excipient.  
     
     
         10 . A method for treating a patient suffering from thrombocytopenia, comprising the step of administrating to the patient an effective amount of the protein according to  claim 1  or having an effective amount of the protein according to  claim 1  expressed in the patient.