Hydrazinyl-Indole Compounds and Methods for Producing a Conjugate

Abstract

The present disclosure provides conjugate structures (e.g., polypeptide conjugates) and hydrazinyl-indole compounds used to produce these conjugates. The disclosure also provides methods of production of such conjugates, as well as methods of using the same.

1 . A conjugate comprising:
 at least one modified amino acid residue of formula (111):   
       
         
           
           
               
               
           
         
         wherein 
         n is 0 or 1; 
         R 1  is selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl; 
         R 2  and R 3  are each independently selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, amino, substituted amino, carboxyl, carboxyl ester, acyl, acyloxy, acyl amino, amino acyl, alkylamide, substituted alkylamide, sulfonyl, thioalkoxy, substituted thioalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl; 
         X 1 , X 2 , X 3  and X 4  are each independently selected from C, N, O and S; 
         Y 1 , Y 2 , Y 3 , and Y 5  are each independently selected from hydrogen, halogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, amino, substituted amino, carboxyl, carboxyl ester, acyl, acyloxy, acyl amino, amino acyl, alkylamide, substituted alkylamide, sulfonyl, thioalkoxy, substituted thioalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl; 
         L is an optional linker, 
         wherein one of W 1  and W 2  is a polypeptide and the other is a drug or a detectable label. 
       
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The conjugate of  claim 1 , wherein n is 1. 
     
     
         5 . The conjugate of  claim 1 , wherein R 2  and R 3  are each independently selected from alkyl and substituted alkyl. 
     
     
         6 . The conjugate of  claim 1 , wherein R 2  and R 3  are each methyl. 
     
     
         7 . The conjugate of  claim 1 , wherein X 1 , X 2 , X 3  and X 4  are each C. 
     
     
         8 . The conjugate of  claim 1 , wherein Y 1 , Y 2 , Y 3  and Y 5  are each H. 
     
     
         9 . The conjugate of  claim 1 , wherein L is present and comprises a group selected from alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, amino, substituted amino, carboxyl, carboxyl ester, acyl amino, alkylamide, substituted alkylamide, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl. 
     
     
         10 . The conjugate of  claim 1 , wherein L is present and comprises a polymer. 
     
     
         11 . The conjugate of  claim 10 , wherein the polymer is a polyethylene glycol. 
     
     
         12 . The conjugate of  claim 1 , wherein the detectable label comprises a fluorophore. 
     
     
         13 . The conjugate of  claim 1 , wherein W 1  is the drug or the detectable label, and W 2  is the polypeptide. 
     
     
         14 . The conjugate of  claim 1 , wherein W 1  is the polypeptide, and W 2  is the drug or the detectable label. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . The conjugate of  claim 1 , wherein the conjugate comprises at least one modified amino acid residue of formula (IIIa): 
       
         
           
           
               
               
           
         
       
     
     
         19 .- 41 . (canceled) 
     
     
         42 . A pharmaceutical composition comprising:
 a conjugate of  claim 1 ; and   a pharmaceutically acceptable excipient.   
     
     
         43 . A method of delivering a conjugate to a subject, the method comprising:
 administering to the subject an effective amount of a conjugate of  claim 1 .   
     
     
         44 . A method of treating a condition in a subject, the method comprising:
 administering to the subject having the condition a therapeutically effective amount of a pharmaceutical composition comprising a conjugate of  claim 1 , wherein the administering is effective to treat the condition in the subject.