Substance p-saporin (sp-sap) conjugates and methods of use

Abstract

This invention provides a conjugate comprising Substance P, or an analog thereof, and a protein, such as Saporin, that inhibits protein synthesis. This invention provides a method of reducing the perception of pain by a subject comprising administering to the subject an effective amount of the pharmaceutical composition of the conjugate comprising Substance 9, or an analog thereof, and a protein such as Saporin that inhibits protein synthesis, so as to reduce the perception of pain by the subject. This invention provides a method of selectively destroying NK-1R-expressing neuronal cells in a subject comprising administering to the subject an effective amount of the conjugate comprising Substance P, or an analog thereof, and a protein such as Saporin that inhibits protein synthesis, so as to selectively destroy NK-1R-expresssing neuronal cells. Lastly, this invention provides a method for treating a NK-1R-associated disorder in a subject, which comprises administering to the subject an amount of the pharmaceutical composition comprising substance P, or an analog thereof, and a protein such as Saporin that inhibits protein synthesis, in an effective amount to treat the disorder associated with the NK-1R.

1 . A conjugate comprising Substance P or an analog thereof, and a protein that inhibits protein synthesis. 
     
     
         2 . The conjugate of  claim 1 , wherein the conjugate comprises an analog of Substance P. 
     
     
         3 . The conjugate of  claim 1 , wherein the Substance P has the amino acid sequence at the N-terminus CYGGGGGGRPKPQQFFSarLMet(0 2 )-amide (SEQ ID NO. 1). 
     
     
         4 . The conjugate of  claim 1 , wherein the Substance P has the amino acid sequence at the N-terminus CYGGGGGGRPKPQQFFGLM-amide (SEQ ID NO. 2). 
     
     
         5 . The conjugate of  claim 1 , wherein the protein is Saporin. 
     
     
         6 . The conjugate of  claim 1 , wherein the protein is in a recombinant form. 
     
     
         7 . A conjugate comprising a protein that inhibits protein synthesis and an antibody that recognizes the NK-1 receptor. 
     
     
         8 . The conjugate of  claim 1 , wherein the protein is ricin A chain, gelonin, pokeweed antiviral protein, or a bacterial toxin, or any fragment thereof, that inhibits protein synthesis. 
     
     
         9 . The conjugate of  claim 1 , wherein the protein is diptheria toxin or  pseudomonas aeruginosa  toxin, or any fragment thereof. 
     
     
         10 . A pharmaceutical composition comprising a therapeutically effective amount of the conjugate of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         11 . A pharmaceutical composition comprising a therapeutically effective amount of the conjugate of  claim 2  and a pharmaceutically acceptable carrier. 
     
     
         12 . A pharmaceutical composition comprising a therapeutically effective amount of the conjugate of  claim 3  and a pharmaceutically acceptable carrier. 
     
     
         13 . A pharmaceutical composition comprising a therapeutically effective amount of the conjugate of  claim 4  and a pharmaceutically acceptable carrier. 
     
     
         14 . A pharmaceutical composition comprising a therapeutically effective amount of the conjugate of  claim 8  and a pharmaceutically acceptable carrier. 
     
     
         15 . A pharmaceutical composition comprising a therapeutically effective amount of the conjugate of  claim 9  and a pharmaceutically acceptable carrier. 
     
     
         16 . A method of reducing the perception of pain by a subject comprising administering to the subject an effective amount of the pharmaceutical composition of  claim 10  so as to reduce the perception of pain by the subject. 
     
     
         17 . A method of reducing the perception of pain by a subject comprising administering to the subject an effective amount of the pharmaceutical composition of  claim 11  so as to reduce the perception of pain by the subject. 
     
     
         18 . A method of reducing the perception of pain by a subject comprising administering to the subject an effective amount of the pharmaceutical composition of  claim 12  so as to reduce the perception of pain by the subject. 
     
     
         19 . A method of reducing the perception of pain by a subject comprising administering to the subject an effective amount of the pharmaceutical composition of  claim 13  so as to reduce the perception of pain by the subject. 
     
     
         20 . A method of reducing the perception of pain by a subject comprising administering to the subject an effective amount of the pharmaceutical composition of  claim 14  so as to reduce the perception of pain by the subject. 
     
     
         21 . A method of reducing the perception of pain by a subject comprising administering to the subject an effective amount of the pharmaceutical composition of  claim 15  so as to reduce the perception of pain by the subject. 
     
     
         22 . A method of selectively destroying NK-1 receptor expressing cells in a subject comprising administering to the subject an effective amount of the conjugate of  claim 1  so as to selectively destroy NK-1 receptor expressing cells. 
     
     
         23 . A method of treating a subject with cancer comprising administering to the subject an effective amount of the pharmaceutical composition of  claim 10  so as to treat the cancer. 
     
     
         24 . A method for treating a NK-1 receptor associated disorder in a subject, which comprises administering to the subject an amount of the pharmaceutical composition of  claim 10  thereby treating the disorder associated with the NK-1 receptor.