Targeted effector proteins and uses thereof
Provided herein are targeted effector fusion proteins, complexes thereof, and uses thereof. The targeted effector fusion proteins can include an effector protein that can be linked to a targeting moiety. Monomer targeted effector fusion proteins can form homogeneous or heterogeneous complexes. The targeted effector fusion proteins and complexes thereof can be formulated as pharmaceutical formulations. The targeted effector fusion proteins, complexes thereof, and formulations thereof can be administered to a subject in need thereof.
1. A targeted effector fusion protein comprising:
an effector protein; and
a targeting moiety, wherein the targeting moiety is operatively linked to the effector protein via a linker,
wherein the linker comprises a polypeptide sequence that is about 90 to 100% identical to any one of SEQ ID NOs: 2-16.
2. The targeted effector fusion protein of claim 1 , wherein the linker is a flexible linker or a rigid linker.
3. The targeted effector fusion protein of claim 2 , wherein the targeting moiety is capable of specifically binding to a carbohydrate.
4. The targeted effector fusion protein of claim 1 , wherein the effector protein is an enzyme.
5. The targeted effector fusion protein of claim 4 , wherein the enzyme is indoleamine 2,3 dioxygenase.
6. The targeted effector fusion protein of claim 1 , wherein the targeting moiety is a galectin protein.
7. The targeted effector fusion protein of claim 6 , wherein the targeting moiety is galectin-3.
8. The targeted effector protein of claim 1 , wherein the linker is an alpha coil polypeptide or a random coil polypeptide.
9. The targeted effector protein of claim 8 , wherein the alpha coil polypeptide comprises one or more heptads, where each heptad has the general formula of AB C D E F G, wherein amino acids A and D are each a hydrophobic amino acid, wherein amino acids B, C, E, F, and G, are each independently selected from a hydrophilic amino acid, a polar amino acid, or a charged amino acid.
10. The targeted effector protein of claim 8 , wherein the alpha coil polypeptide is capable of multimerizing with one or more other alpha coils that are integrated in one or more other targeted effector proteins.
11. The targeted effector fusion protein of claim 8 , wherein the targeting moiety is capable of specifically binding to a carbohydrate.
12. The targeted effector fusion protein of claim 8 , wherein the effector protein is an enzyme.
13. The targeted effector fusion protein of claim 12 , wherein the enzyme is indoleamine 2,3 dioxygenase.
14. The targeted effector fusion protein of claim 8 , wherein the targeting moiety is a galectin protein.
15. The targeted effector fusion protein of claim 14 , wherein the targeting moiety is galectin-3.
16. A multimeric targeted effector fusion protein complex comprising:
at least two targeted effector fusion proteins according to claim 8 , wherein the at least two targeted effector proteins are conjugated to each other by binding between the alpha coil polypeptide or random coil polypeptide in each of the at least two targeted effector proteins.
17. The multimeric targeted effector fusion protein complex of claim 16 , wherein the multimeric targeted effector fusion protein complex is homogeneous.
18. The multimeric targeted effector fusion protein complex of claim 16 , wherein the multimeric targeted effector fusion protein complex is heterogeneous.
19. A pharmaceutical formulation comprising:
a targeted effector fusion protein as in claim 1 ; and
a pharmaceutically acceptable carrier.
20. A pharmaceutical formulation comprising:
a multimeric targeted effector fusion protein complex as in claim 16 ; and
a pharmaceutically acceptable carrier.
21. A targeted effector fusion protein comprising:
an effector protein; and
a targeting moiety, wherein the targeting moiety is operatively linked to the effector protein via a linker,
wherein the effector protein is indoleamine 2,3 dioxygenase, and wherein the targeting moiety is a galectin protein.
22. The targeted effector fusion protein of claim 21 , wherein the targeting moiety is galectin-3.
23. The targeted effector protein of claim 21 , wherein the linker is an alpha coil polypeptide or a random coil polypeptide.
24. A multimeric targeted effector fusion protein complex comprising:
at least two targeted effector fusion proteins according to claim 23 , wherein the at least two targeted effector proteins are conjugated to each other by binding between the alpha coil polypeptide or random coil polypeptide in each of the at least two targeted effector proteins.
25. The multimeric targeted effector fusion protein complex of claim 24 , wherein the multimeric targeted effector fusion protein complex is homogeneous.
26. The multimeric targeted effector fusion protein complex of claim 24 , wherein the multimeric targeted effector fusion protein complex is heterogeneous.