Water Soluble Cholesterol Derivatives

Abstract

Four novel water soluble cholesterol derivative compounds are disclosed. These compounds have various applications in studies of membrane proteins, including drug screening and studies of receptor stability and folding. In one aspect the water soluble cholesterol derivatives disclosed may be used to replace cholesterol in micelle-solubilized membrane protein preparations.

What is claimed is: 
     
         1 . Cholesterol-β-tetrasaccharide according to Formula I: 
       
         
           
           
               
               
           
         
       
     
     
         2 . Cholesterol-α-tetrasaccharide according to Formula II: 
       
         
           
           
               
               
           
         
       
     
     
         3 . Cholesterol-β-sulfated maltoside according to Formula III, wherein X is selected from the group consisting of Me 3 NH, NH 4 , and Na: 
       
         
           
           
               
               
           
         
       
     
     
         4 . Diosgenin-β-tetrasaccharide according to Formula IV: 
       
         
           
           
               
               
           
         
       
     
     
         5 . A composition comprising the cholesterol-β-tetrasaccharide according to  claim 1 . 
     
     
         6 . A composition comprising the cholesterol-α-tetrasaccharide according to  claim 2 . 
     
     
         7 . A composition comprising the cholesterol-β-sulfated maltoside according to  claim 3 . 
     
     
         8 . A composition comprising the diosgenin-β-tetrasaccharide according to  claim 4 . 
     
     
         9 . A method of synthesizing the cholesterol-β-tetrasaccharide according to  claim 1 , wherein the synthesis begins with materials comprising cholesterol and maltose. 
     
     
         10 . A method of synthesizing the cholesterol-α-tetrasaccharide according to  claim 2 , wherein the synthesis begins with materials comprising cholesterol and maltose. 
     
     
         11 . A method of synthesizing the cholesterol-β-sulfated maltoside according to  claim 3 , wherein the synthesis begins with materials comprising cholesterol and maltose. 
     
     
         12 . A method of synthesizing the diosgenin-β-tetrasaccharide according to  claim 4 , wherein the synthesis begins with materials comprising diosgenin and maltose. 
     
     
         13 . A method of reconstituting membrane proteins in a lipid bilayer, comprising:
 providing membrane protein;   providing at least one cholesterol derivative selected from the group consisting of:   
       
         
           
           
               
               
           
         
       
       and mixing the membrane protein and the at least one cholesterol derivative to reconstitute membrane protein suitable for in vitro biochemical and structural studies. 
     
     
         14 . The method according to  claim 13 , wherein the membrane protein is a G-protein coupled receptor (GPCR). 
     
     
         15 . The method according to  claim 13 , wherein the membrane protein is a transmembrane protein.