Dendritic Molecular Intracellular Transporters and Methods of Making and Using Same

Abstract

In accordance with the purpose(s) of the invention, as embodied and broadly described herein, the invention, in one aspect, relates to compounds comprising the structure: and at least one guanidinium residue, wherein m is zero or a positive integer. Also disclosed are methods of preparing the disclosed compounds. Also disclosed are methods of intracellular delivery comprising administering the disclosed compounds and compositions to a subject. Also disclosed are pharmaceutical compositions comprising a therapeutically effective amount of one or more compounds or compositions of the invention and a pharmaceutically acceptable carrier. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

What is claimed is: 
     
         1 . A compound comprising the structure: 
       
         
           
           
               
               
           
         
       
       and
 at least one guanidinium residue, 
 wherein m is zero or a positive integer. 
 
     
     
         2 . The compound of  claim 1 , comprising the structure: 
       
         
           
           
               
               
           
         
         wherein n and o are, independently, zero or a positive integer; 
         wherein R 1  and R 2  are, independently, hydrogen, oxygen, alkyl, acyl, thioacyl, or carbonyl; 
         wherein R 3  is hydrogen, alkyloxycarbonyl, or alkyl; 
         R 4  is hydrogen, or alkyloxycarbonyl; 
         wherein R 5  and R 6  are, independently, hydrogen, or alkyl; and 
         wherein R 7  is hydrogen or alkyloxycarbonyl. 
       
     
     
         3 . The compound of  claim 2 , comprising the structure: 
       
         
           
           
               
               
           
         
         wherein n is an integer from 1 to 9; 
         wherein R 1  and R 2  are, independently, hydrogen, oxygen, nitrogen, alkyl, acyl, thioacyl, carbonyl, or amine; 
         wherein R 3  is hydrogen or alkyl; and 
         wherein R 4  is hydrogen, or alkyloxycarbonyl, alkyl, or acyl. 
       
     
     
         4 . The compound of  claim 2 , comprising the structure: 
       
         
           
           
               
               
           
         
         wherein n is an integer from 1 to 9; 
         wherein R 1  and R 2  are, independently, hydrogen, amino, hydroxyl, alkyl, alkoxyl, acyl, carbonyl, or thioacyl; 
         wherein R 3  is hydrogen or alkyl; and 
         wherein R 4  is hydrogen, or alkyloxycarbonyl. 
       
     
     
         5 . A method of preparing a compound having the structure: 
       
         
           
           
               
               
           
         
         wherein n is an integer from 1 to 9, 
         wherein R 3  is hydrogen or alkyl, 
         wherein R 4  and R 7  are, independently, hydrogen, alkyloxycarbonyl, alkyl, or acyl; 
         wherein R 7  is hydrogen, alkyl, or acyl; 
         wherein Y comprises a nitro group, an amine group, an amide group, azide group, or an alkyloxycarbonyl protected amine group or a derivative thereof, 
         the method comprising the steps of:
 a. providing a first compound comprising the structure: 
 
       
       
         
           
           
               
               
           
         
         wherein X comprises OH, halogen, or OC(O)-alkyl;
 b. coupling the first compound with at least about three molar equivalents of a second compound comprising the structure: 
 
       
       
         
           
           
               
               
           
         
         wherein G 1  is an ester-protecting group;
 c. removing the ester-protecting group; 
 d. reacting the product of step (c) with at least about three molar equivalents of a third compound comprising the structure: 
 
       
       
         
           
           
               
               
           
         
         wherein G 2  is an amine-protecting group;
 e. removing the amine-protecting group; and 
 f. functionalizing the product of step (e) with at least three molar equivalents of a guanidine-providing agent. 
 
       
     
     
         6 . The method of  claim 5 , further comprising the step of transforming Y into an amine to provide a compound comprising the structure: 
       
         
           
           
               
               
           
         
       
     
     
         7 . The method of  claim 5 , further comprising the step of acylating the amine with a compound comprising the structure: 
       
         
           
           
               
               
           
         
         wherein o and p are, independently, zero or a positive integer. 
       
     
     
         8 . The method of  claim 5 , further comprising the step of acylating the amine with a compound comprising the structure: 
       
         
           
           
               
               
           
         
         wherein o and p are, independently, zero or a positive integer, and 
         wherein G 3  is an thiol-protecting group. 
       
     
     
         9 . The method of  claim 8 , wherein the thiol protecting group comprises the structure: 
       
         
           
           
               
               
           
         
       
       and
 wherein the fourth compound comprises the structure: 
 
       
         
           
           
               
               
           
         
       
     
     
         10 . The product of the method of  claim 5 . 
     
     
         11 . An intracellular delivery composition comprising the general structure:
   P-L-B—F,
   wherein P is payload moiety;   wherein L is a linking moiety comprising the structure:   
       
         
           
           
               
               
           
         
         wherein o and p are, independently, zero or a positive integer; 
         wherein B is a branching moiety comprising the structure: 
       
       
         
           
           
               
               
           
         
       
       and
 wherein F is a functional moiety comprising at least one guanidinium residue. 
 
     
     
         12 . The composition of  claim 11 , comprising at least six guanidinium residues. 
     
     
         13 . The composition of  claim 11 , wherein the payload moiety comprises a luminescent group, a biologically-active group, or a pharmaceutically-active group. 
     
     
         14 . The composition of  claim 11 , wherein L-B—F comprises the structure: 
       
         
           
           
               
               
           
         
         wherein n is an integer from 1 to 9; 
         wherein R 3  is hydrogen or alkyl; 
         wherein R 4  is hydrogen, alkyl or acyl; and 
         wherein R 7  is hydrogen, alkyl or acyl. 
       
     
     
         15 . A method of intracellular delivery comprising administering an effective amount of a compound of  claim 1  to a subject. 
     
     
         16 . A pharmaceutical composition comprising a therapeutically effective amount of one or more compounds of  claim 1  and a pharmaceutically acceptable carrier for administration in a mammal. 
     
     
         17 . A block copolymer comprising the structure A-B,
 wherein A is an oligomeric block comprising at least two reactive residues, and   wherein B is a block comprising at least one functional moiety.   
     
     
         18 . The block copolymer of  claim 17 , wherein the functional moiety comprises a semiconducting moiety, an imaging moiety, or a drug-delivery moiety. 
     
     
         19 . A method of nanoparticle formation comprising the steps of:
 a. providing a reactor capable of imparting a stimulus and   b. adding to the reactor a block copolymer comprising at least two reactive residues, thereby imparting the stimulus on at least a portion of the block copolymer;   wherein the at least two reactive residues form reactive intermediates upon exposure to the stimulus, and   wherein the reactive intermediates are capable of undergoing a bond-forming reaction.   
     
     
         20 . The product of the method of  claim 19 .