Cell internalizing compounds

Abstract

Provided herein are cell penetrating compounds having the Formula I: where, generally, each T is a thiol reactive group (e.g., a phosphorothioate), each L is a linker (e.g., a linear alkyl), and Y is a biologic (e.g., an antibody). Also provided are pharmaceutical compositions including the cell penetrating compounds, and methods of delivering the compound into a cell.

1 .- 22 . (canceled) 
     
     
         23 . A compound having the Formula III: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         L is a linker; 
         n is an integer from 1 to 3; 
         m is an integer from 5 to 25; and 
         Y is a protein, an antibody, a peptide, or a nucleic acid. 
       
     
     
         24 . The compound of  claim 23 , wherein m is 15-20. 
     
     
         25 . The compound of  claim 24 , wherein m is 16, 17 or 18. 
     
     
         26 . The compound of  claim 23 , wherein L is a PEG, a linear alkyl, or a cyclic alkyl. 
     
     
         27 . The compound of  claim 26 , wherein L is a linear (C 2 -C 10 )alkyl, or —(O—CH 2 —CH 2 ) p —, wherein p is an integer from 1 to 5. 
     
     
         28 . A compound having the Formula IV: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein:
 L is a linker group; 
 Y is a protein, an antibody, a peptide, or a nucleic acid; and 
 n is an integer from 5 to 25. 
 
       
     
     
         29 . The compound of  claim 28 , wherein n is an integer from 15-20. 
     
     
         30 . The compound of  claim 29 , wherein n is 16, 17 or 18. 
     
     
         31 . The compound of  claim 28 , wherein L is a PEG, a linear alkyl, or a cyclic alkyl. 
     
     
         32 . The compound of  claim 31 , wherein Lisa linear (C 2 -C 10 )alkyl, a (C 5 -C 6 )cyclic alkyl, or —(O—CH 2 —CH 2 ) p —, wherein p is an integer from 1 to 5. 
     
     
         33 . The compound of  claim 31 , wherein Lisa linear (C 3 -C 6 )alkyl. 
     
     
         34 . A compound having the Formula V: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein:
 L is a linker; 
 Y is a protein, an antibody, a peptide, or a nucleic acid; 
 n is an integer from 5 to 25; and 
 each R is independently selected from: 
 
       
       
         
           
           
               
               
           
         
       
     
     
         35 . The compound of  claim 34 , wherein n is an integer from 15 to 20. 
     
     
         36 . The compound of  claim 35 , wherein n is 16, 17 or 18. 
     
     
         37 . The compound of  claim 34 , wherein L is a PEG, a linear alkyl, or a cyclic alkyl. 
     
     
         38 . The compound of  claim 37 , wherein L is a linear (C 2 -C 10 )alkyl, a cyclic (C 5 -C 6 )alkyl, or —(O—CH 2 —CH 2 ) p —, wherein p is an integer from 1 to 5. 
     
     
         39 . The compound of  claim 38 , wherein L is a linear (C 3 -C 6 )alkyl. 
     
     
         40 . The compound of  claim 23 , wherein Y is an antibody or antibody fragment. 
     
     
         41 . The compound of  claim 23 , wherein Y is a peptide. 
     
     
         42 . The compound of  claim 23 , wherein Y is a protein. 
     
     
         43 . The compound of  claim 23 , wherein Y is a nucleic acid. 
     
     
         44 . A pharmaceutical composition comprising the compound of  claim 23 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier. 
     
     
         45 . A method of delivering a therapeutic agent into a cell comprising contacting a cell with a compound of  claim 23 , wherein the compound is internalized into the cell.