Hydrazinyl-indole compounds and methods for producing a conjugate
View Patent ↗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 (I):
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 is C or N, wherein if X 1 is N, then Y 1 is absent;
X 2 , X 3 and X 4 are each C;
X 5 is C;
Y 1 , Y 2 , Y 3 , Y 4 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;
Q 1 is a bond to X 5 and Y 5 is absent; and
L is an optional linker,
wherein W 2 is a polypeptide comprising a converted sulfatase motif and W 1 is a drug or a detectable label.
2. The conjugate of claim 1 , wherein n is 1.
3. The conjugate of claim 1 , wherein R 2 and R 3 are each independently selected from alkyl and substituted alkyl.
4. The conjugate of claim 1 , wherein R 2 and R 3 are each methyl.
5. The conjugate of claim 1 , wherein Y 1 , Y 2 , Y 3 and Y 4 are each H.
6. 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.
7. The conjugate of claim 1 , wherein L is present and comprises a polymer.
8. The conjugate of claim 7 , wherein the polymer is a polyethylene glycol.
9. The conjugate of claim 1 , wherein the detectable label comprises a fluorophore.
10. The conjugate of claim 1 , wherein the conjugate comprises at least one modified amino acid residue of formula (II):
11. The conjugate of claim 1 , wherein the conjugate comprises at least one modified amino acid residue of formula (IIa):
12. A pharmaceutical composition comprising:
a conjugate of claim 1 ; and
a pharmaceutically acceptable excipient.
13. 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 .