Anti-inflammatory, tolerogenic and immunoinhibiting properties of carbohydrate binding-peptides

Abstract

The present invention is directed to methods of suppressing inflammatory responses, inducing tolerance to an antigen, and suppressing cell adhesion, e.g., involved in metastasis, by the administration of lectin derived carbohydrate binding peptides or derivatives thereof, in particular, peptides capable of binding terminally linked α-sialic acid(2→6)βGal- and/or α-sialic acid(2→3)βGal-groups on structures or molecules comprising such groups. Pharmaceutical compositions containing such lectin derived carbohydrate binding peptides or derivatives thereof are also disclosed.

What is claimed is:  
     
         1 . A method of suppressing a inflammatory response in a mammal by the administration of an effective amount of at least one lectin derived carbohydrate binding peptide or derivative thereof capable of binding a terminally linked α-sialic acid(2→6)βGal- and/or α-sialic acid(2→3)βGal- groups on structures or molecules comprising such groups.  
     
     
         2 . The method of  claim 1 , where said inflammatory response arises from antigen challenge in a sensitized mammal.  
     
     
         3 . The method of  claim 2 , wherein said antigen challenge is selected from the group consisting of delayed type hypersensitivity (DTH), rheumatoid arthritis, psoriasis, asthma, dermatitis, inflammatory bowel disease, multiple sclerosis, viral pneumonia, and bacterial pneumonia.  
     
     
         4 . The method of  claim 1 , wherein said inflammatory response is associated with mammalian injury.  
     
     
         5 . The method of  claim 4 , wherein said injury is selected from the group consisting of acute respiratory distress syndrome (ARDS), reperfusion injury frost bite, and septic shock.  
     
     
         6 . The method of  claim 1 , wherein said carbohydrate binding peptide or derivative thereof is administered after initiation of the mammal's inflammatory response but at or prior to one-half the period required for maximal inflammation.  
     
     
         7 . The method of  claim 1 , wherein the lectin derived carbohydrate binding peptide is selected from the group of peptides set forth in FIG. 1.  
     
     
         8 . The method of  claim 1 , wherein said lectin derived carbohydrate binding peptide is selected from the group consisting of formula I 
       SPX 1 GX 2 C  I where X 1  is selected from the group of amino acids Y, F, W, and H or peptide mimetics thereof, and X 2  is selected from the group consisting of amino acids Y, F, R, W, and H or peptide mimetics thereof;    and formula II:   SPX 1 GX 2 CX 3 X 4   II   where X 1  is selected from the group of amino acids Y, F, W, and H or peptide mimetics thereof,    X 2  is selected from the group consisting of amino acids Y, F, R, W, and H or peptide mimetics thereof;    X 3  is an amino acid sequence of 4-6 amino acids; and    X 4  is selected from the group consisting of amino acids Y, F, W, and H or peptide mimetics thereof.    
     
     
         9 . The method of  claim 8 , wherein said lectin derived carbohydrate binding peptide is SPYGRC.  
     
     
         10 . The method of  claim 1 , wherein said lectin derived carbohydrate binding peptide is administered at a dosage ranging from about 0.5 to 50 mg/kg body weight.  
     
     
         11 . The method of  claim 10 , wherein said lectin derived carbohydrate binding protein or derivative thereof is administered parenterally, orally, intranasally, intratracheally or transdermally.  
     
     
         12 . The method of  claim 10 , wherein said lectin derived carbohydrate binding protein or derivative thereof is administered intravenously or intramuscularly.  
     
     
         13 . A method for modulating the induction of an immune response to an antigen in a mammal by administering the antigen in combination with an effective amount of at least one lectin derived carbohydrate binding peptide or derivative thereof capable of binding terminally linked α-sialic acid(2→6)βGal- and/or α-sialic acid(2→3)βGal- groups on structures or molecules comprising such groups.  
     
     
         14 . The method of  claim 13 , wherein said immune response comprises a humoral or cell mediated immune response.  
     
     
         15 . The method of  claim 13 , wherein the antigen comprises an allergen.  
     
     
         16 . The method of  claim 13 , wherein the dosage of said at least one lectin derived carbohydrate binding peptide or derivative thereof ranges from about 0.5 to 50 mg/kg of body weight.  
     
     
         17 . A method for inducing, in a sensitized mammal, long term tolerance to an antigen by challenging said mammal with the antigen and followed by administering an effective amount at least one lectin derived carbohydrate binding peptide or derivative thereof capable of binding terminally linked α-sialic acid(2→6)βGal- and/or α-sialic acid(2→3)βGal- groups on structures or molecules comprising such groups.  
     
     
         18 . The method of  claim 17 , wherein the antigen comprises an allergen.  
     
     
         19 . The method of  claim 17 , wherein the administrtion of said lectin derived carbohydrate binding peptide or derivative thereof is after initiation of the mammal's inflammatory response to said antigen challenge but at or prior to one-half the period required for maximal inflammation to the antigen challenge.  
     
     
         20 . The method of  claim 19 , wherein the amount of the lectin derived carbohydrate binding peptide or derivative thereof which is administered ranges from about 0.5 to 50 mg/kg of body weight.  
     
     
         21 . A method for treating lung inflammation and/or lung injury in a mammal by administering an effective amount of one or more lectin derived carbohydrate binding peptides or derivative thereof capable of binding terminally linked α-sialic acid(2→6)βGal- and/or α-sialic acid(2→3)βGal- groups on structures or molecules comprising such groups.  
     
     
         22 . The method of  claim 21 , wherein the mammalian lung inflammation or lung injury comprises acute respiratory distress syndrome (ARDS).  
     
     
         23 . The method of  claim 22 , wherein the administration of said lectin derived carbohydrate binding peptide or derivative thereof is by parenteral, intratracheal, intranasal, oral or transdermal routes.  
     
     
         24 . The method of  claim 21 , wherein the amount of the lectin derived carbohydrate binding peptide or derivative thereof which is administered ranges from about 0.5 to 50 mg/kg of body weight.  
     
     
         25 . A method for inhibiting metastasis of tumor cells in a mammal by administering an effective amount at least one lectin derived carbohydrate binding peptide or derivative thereof capable of binding terminally linked α-sialic acid(2→6)βGal- and/or α-sialic acid(2→3)βGal- groups on structures or molecules comprising such groups.  
     
     
         26 . The method of  claim 25 , wherein the administration is effected in a mammal before, during, or after a cancer surgery or biopsy.  
     
     
         27 . The method of  claim 26 , wherein the administration is effected at a time ranging from about 5 hours before cancer surgery or biopsy to about 15 hours after cancer surgery or biopsy.  
     
     
         28 . The method of  claim 26 , wherein the cancer comprises colon carcinoma or melanoma.  
     
     
         29 . A method for inhibiting infection in mammalian hosts by bacterial/viral agents and/or their toxins which employ terminally linked α-sialic acid(2→6)βGal- and/or α-sialic acid(2→3)βGal- structures as the receptor site on a cell of the targeted mammalian host which method comprises administering to the mammal an effective amount at least one lectin derived carbohydrate binding peptide or derivative thereof capable of binding terminally linked α-sialic acid(2→6)βGal- and/or α-sialic acid(2→3)βGal- groups on structures or molecules comprising such groups.