Shk-based pharmaceutical compositions and methods of manufacturing and using the same

Abstract

Disclosed herein are pharmaceutical compositions having the sequence Arg-Ser-Cys-Ile-Asp-Thr-Ile-Pro-Lys-Ser-Arg-Cys-Thr-Ala-Phe-Gln-Cys-Lys-His-Ser-Xaa-Lys-Tyr-Arg-Leu-Ser-Phe-Cys-Arg-Lys-Thr-Cys-Gly-Thr-Cys (SEQ ID NO:1). The disclosed compositions can include an acid or amide at the C-terminus of SEQ ID NO:1 and the polypeptide can be attached to an organic or inorganic chemical entity that has an anionic charge. The polypeptide can be detectably labeled for diagnostic purposes. Methods of manufacturing and using the pharmaceutical compounds are also disclosed.

What is claimed is: 
     
         1 . A pharmaceutical composition suitable for diagnostic in vivo use comprising a pharmaceutically acceptable salt of a ShK polypeptide having the sequence Arg-Ser-Cys-Ile-Asp-Thr-Ile-Pro-Lys-Ser-Arg-Cys-Thr-Ala-Phe-Gln-Cys-Lys-His-Ser-Xaa-Lys-Tyr-Arg-Leu-Ser-Phe-Cys-Arg-Lys-Thr-Cys-Gly-Thr-Cys (SEQ ID NO:1) wherein the ShK polypeptide is attached to a detectable label and an organic or inorganic chemical entity that has an anionic charge, and wherein the C-terminus is an acid or an amide. 
     
     
         2 . The composition of  claim 1  wherein said detectable label is a chelate of Indium-111 (In 111 ). 
     
     
         3 . The composition of  claim 2  wherein said detectable label is a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-chelate of Indium-111 (In 111 ). 
     
     
         4 . The composition of  claim 1  wherein said detectable label is a chelate of gadolinium (Gd). 
     
     
         5 . The composition of  claim 4  wherein said detectable label is a DOTA-chelate of gadolinium (Gd). 
     
     
         6 . The composition of  claim 1  wherein said ShK polypeptide has the sequence Tyr-AEEA-Arg-Ser-Cys-Ile-Asp-Thr-Ile-Pro-Lys-Ser-Arg-Cys-Thr-Ala-Phe-Gln-Cys-Lys-His-Ser-Met-Lys-Tyr-Arg-Leu-Ser-Phe-Cys-Arg-Lys-Thr-Cys-Gly-Thr-Cys-NH 2  (SEQ ID NO: 5) and the detectable label is at the amino terminus. 
     
     
         7 . The composition of  claim 6  wherein the detectable label is a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-chelate of Indium-111 (In 111 ).