Novel haptotactic peptides

Abstract

Novel cell attachment peptides having sequences homologous to specific portions of the carboxy terminal sequence of fibrinogen chains are disclosed. The novel peptides, derived from proteins related to fibrinogen including a peptide adjacent to fibrinogen γ-chain C terminus denoted pre-Cγ possess cell attraction activities, and are useful in pharmaceutical compositions.

1 - 32 . (canceled) 
     
     
         33 . An isolated haptotactic peptide the sequence of which comprises an amino acid sequence as set forth in any one of SEQ ID NOs:2-4, 6-10, characterized in that the haptotactic peptide induces cell attachment to a surface to which said haptotactic peptide is covalently bound, wherein the number of cells which attach to the surface is at least 50% greater than the number of cells attached to said surface in the absence of said peptide. 
     
     
         34 . A composition comprising the isolated haptotactic peptide of  claim 33 . 
     
     
         35 . The composition of  claim 34 , wherein said composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier. 
     
     
         36 . The pharmaceutical composition of  claim 35 , further comprising at least one additional drug or biological agent. 
     
     
         37 . A composition comprising the isolated haptotactic peptide of  claim 33 , wherein said peptide is covalently attached to a substance selected from the group consisting of a drug, a medical device, a bead and a matrix. 
     
     
         38 . The composition of  claim 37 , wherein the haptotactic peptide is covalently attached to the surface of a medical device. 
     
     
         39 . The composition of  claim 38 , wherein the medical device is a medical implant. 
     
     
         40 . The composition of  claim 37 , wherein the haptotactic peptide is covalently attached to a bead. 
     
     
         41 . The composition of  claim 37 , wherein the haptotactic peptide is covalently attached to a matrix. 
     
     
         42 . The composition of  claim 37 , wherein the haptotactic peptide is covalently attached to a drug. 
     
     
         43 . The pharmaceutical composition of  claim 35 , further comprising at least one additional isolated haptotactic peptide. 
     
     
         44 . The pharmaceutical composition of  claim 35 , further comprising a plurality of cells selected from the group consisting of mesenchymal cells, parenchymal cells, fibroblasts, endothelial cells, chondrocytes, kidney cells, liver cells, pancreatic cells, thyroid cells, glial cells, astrocytes, smooth muscle cells and myofibroblasts. 
     
     
         45 . The pharmaceutical composition of  claim 35 , further comprising a plurality of cells selected from the group consisting of immortalized cells, transformed cells, mammary carcinoma cells, 3T3 fibroblasts, malignant melanoma cells and ovarian carcinoma cells. 
     
     
         46 . The pharmaceutical composition of  claim 35 , further comprising a plurality of pluripotent cells capable of differentiating into cells selected from fibroblasts, myofibroblasts, smooth muscle cells, endothelial cells, and combinations thereof. 
     
     
         47 . The pharmaceutical composition of  claim 35 , further comprising a plurality of cells selected from the group consisting of neural cells, glial cells, astrocytes, and combinations thereof. 
     
     
         48 . The pharmaceutical composition of  claim 35 , further comprising a plurality of cells selected from the group consisting of cells derived from bone marrow, blood or buff-coat capable of differentiating into osteoblasts, chrondrocytes, and combinations thereof. 
     
     
         49 . The composition of  claim 45 , wherein the plurality of cells is selected from the group consisting of immortalized cells and hybridomas. 
     
     
         50 . A polymer composition, comprising:
 a plurality of subunits, each of the subunits comprising at least one haptotactic peptide selected from the group consisting of SEQ ID NOs:1-10, further comprising a plurality of linker moieties for covalently linking said plurality of subunits to form the polymer.   
     
     
         51 . An antibody capable of binding a haptotactic peptide, wherein the sequence of the haptotactic peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:1-10. 
     
     
         52 . An isolated polynucleotide encoding a haptotactic peptide the sequence of which is selected from the group consisting of SEQ ID NOs:1-10. 
     
     
         53 . A diagnostic composition comprising the haptotactic peptide of  claim 33 , wherein said haptotactic peptide is linked to a tag selected from the group consisting of a fluorescent tag and a radioactive tag. 
     
     
         54 . The diagnostic composition of  claim 53  wherein the haptotactic peptide is derivatized with a fluorescent tag. 
     
     
         55 . The diagnostic composition of  claim 53  wherein the haptotactic peptide is derivatized with a radioactive tag. 
     
     
         56 . The diagnostic composition of  claim 53  for in vivo imaging and diagnosis of embolisms. 
     
     
         57 . A method of treating a patient comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of  claim 35 . 
     
     
         58 . The method of  claim 57  wherein the patient has a wound and the composition is for enhancing wound healing. 
     
     
         59 . The method of  claim 57  wherein the patient is in need of enhanced osteogenesis and the composition is for enhancing osteogenesis. 
     
     
         60 . The method of  claim 57  wherein the patient is in need of modulated angiogenesis and the composition is for modulating angiogenesis in vivo. 
     
     
         61 . The isolated haptotactic peptide of  claim 33 , wherein said peptide is synthetic peptide. 
     
     
         62 . A device comprising the isolated haptotactic peptide of  claim 33 , wherein said haptotactic peptide is covalently attached to the surface of the device.