IL-2RBETA binding compounds

1. An IL-2Rβ ligand, wherein the IL-2Rβ ligand comprises an amino acid sequence selected from any one of SEQ ID NOS: 589 and 808:

SEQ ID NO: 589

L V G W N H Y D C S V A R V G E L C D L

SEQ ID NO: 808

W Y P C W M A Q L G E L C D L D

wherein each amino acid sequence independently comprises from 1 to 5 of the following conservative substitutions: amino acids having a small hydrophobic side chain comprising alanine (A), glycine (G), proline (P), serine (S), or threonine (T); amino acids having a hydroxyl-containing side chain comprising serine (S), threonine (T), or tyrosine (Y); amino acids having an acidic side chain comprising aspartate (D) or glutamate (E); amino acids having a polar-neutral side chain comprising histidine (H), asparagine (N), glutamine (Q), serine (S), threonine (T), or tyrosine (Y); amino acids having a basic side chain comprising arginine (R), lysine (K), or histidine (H); amino acids having a large hydrophobic side chain comprising isoleucine (I), leucine (L), methionine (M), valine (V), phenylalanine (F), tyrosine (Y), or tryptophan (W); and amino acids having an aromatic side chain comprising phenylalanine (F), histidine (H), tryptophan (W), or tyrosine (Y).

2. The IL-2β ligand of claim 1 , wherein the IL-2Rβ ligand exhibits a binding affinity (IC 50 ) to the human IL-2Rβ subunit of less than 100 μM.

3. The IL-2Rβ ligand of claim 1 , wherein the amino acid sequence is terminated with amino acids -G-G- on the N-terminus, on the C-terminus, or on both the N- and C-termini.

4. A pharmaceutical composition comprising the IL-2Rβ ligand of claim 1 .

5. A compound comprising at least one IL-2Rβ ligand of claim 1 .

6. The compound of claim 5 , wherein the compound is selected from a peptide comprising the IL-2Rβ ligand, a conjugate, and a fusion protein.

7. The compound of claim 5 , wherein the compound comprises an IL-2Rα ligand, an IL-2Rγc ligand, or both an IL-2Rα ligand and an IL-2Rγc ligand.

8. A pharmaceutical composition comprising the compound of claim 5 .

9. An IL-2β ligand comprising the amino acid sequence of Formula (10) (SEQ ID NO: 578):

—X 191 —X 192 —X 193 —X 194 —X 195 —C—X 196 —X 197 —X 198 —X 199 —X 200 —X 201 —X 202 —X 203 —X 204 —X 205 —X 206 —X 207 —X 208 —  (10)

wherein,

X 191 is selected from F, H, I, L, M, V, W, and Y;

X 192 is selected from A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, and Y;

X 193 is selected from F, H, I, L, M, V, W, and Y;

X 194 is selected from F, H, L, W, and Y;

X 195 is selected from D, E, and P;

X 196 is selected from F, H, R, W, and Y;

X 197 is selected from F, I, L, M, and V;

X 198 is A;

X 199 is selected from H, K, Q, N, and R;

X 200 is selected from I, L, and V;

X 201 is G;

X 202 is selected from D, E, and Q;

X 203 is L;

X 204 is selected from D and E;

X 205 is selected from F, I, L, M, V, and W;

X 206 is selected from D, E, F, H, I, L, M, V, W, and Y;

X 207 is selected from A, C, D, E, F, G, H, I, L, M, N, P, Q, R, S, T, V, W, and Y; and

X 208 is selected from D and E.

10. The IL-2β ligand of claim 9 , wherein the IL-2Rβ ligand exhibits a binding affinity (IC 50 ) to the human IL-2Rβ subunit of less than 100 μM.

11. A pharmaceutical composition comprising the IL-2Rβ ligand of claim 9 .

12. A compound comprising at least one IL-2Rβ ligand of claim 9 .

13. The compound of claim 12 , wherein the compound comprises an IL-2Rα ligand, an IL-2Rγc ligand, or both an IL-2Rα ligand and an IL-2Rγc ligand.

14. A pharmaceutical composition comprising the compound of claim 12 .

15. An IL-2β ligand comprising the amino acid sequence of Formula (10) (SEQ ID NO: 578):

—X 191 —X 192 —X 193 —X 194 —X 195 —C—X 196 —X 197 —X 198 —X 199 —X 200 —X 201 —X 202 —X 203 —X 204 —X 205 —X 206 —X 207 —X 208 —  (10)

wherein,

X 191 is selected from F, H, I, L, M, V, W, and Y;

X 192 is selected from A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, and Y;

X 193 is selected from F, H, I, L, M, V, W, and Y;

X 194 is selected from H, L, and Y;

X 195 is selected from D and P;

X 196 is selected from H, R, and W;

X 197 is selected from I and M;

X 198 is A;

X 199 is selected from H, K, Q, and R;

X 200 is selected from L and V;

X 201 is G;

X 202 is selected from D, E, and Q;

X 203 is L;

X 204 is selected from D and E;

X 205 is L;

X 206 is selected from D, E, F, H, I, L, M, V, W, and Y;

X 207 is selected from A, C, D, E, F, G, H, I, L, M, N, P, Q, R, S, T, V, W, and Y; and

X 208 is selected from D and E.

16. The IL-2Rβ ligand of claim 15 , wherein,

X 194 is Y;

X 195 is selected from D and P;

X 196 is W;

X 197 is M;

X 198 is A;

X 199 is Q;

X 199 is selected from H, K, and R;

X 200 is selected from L and V;

X 201 is G;

X 202 is E;

X 203 is L;

X 204 is selected from D and E; and

X 205 is L.

17. The IL-2Rβ ligand of claim 15 , wherein,

X 194 is Y;

X 195 is selected from D and P;

X 196 is selected from H, R, and W;

X 197 is M;

X 198 is A;

X 199 is selected from H, K, Q, and R;

X 200 is selected from L and V;

X 201 is G;

X 202 is E;

X 203 is L;

X 204 is D; and

X 205 is L.

18. A pharmaceutical composition comprising the IL-2Rβ ligand of claim 15 .

19. A compound comprising at least one IL-2Rβ ligand of claim 15 .

20. The compound of claim 19 , wherein the compound comprises an IL-2Rα ligand, an IL-2Rγc ligand, or both an IL-2Rα ligand and an IL-2Rγc ligand.

21. A pharmaceutical composition comprising the compound of claim 19 .

22. An IL-2Rβ ligand, wherein the IL-2Rβ ligand comprises an amino acid sequence selected from any one of SEQ ID NOS: 580-583, 587, 590, 593, 595, 598, 599, 601-603, 605-607, 610-613, 618-620, 626-628, 631, 633, 635, 637, 639, 642, 644, 646-648, 654-656, 659, 661, 663, 665, 666, 669, 674, 681, 682-684, 692, 695, 701, 706, 710, 711, 714-719, 724, 725, 728, 730, 731, 733, 734, 737, 738, 740-742, 747-749, 752-757, 759, 760, 763, 766, 769, 771, 772, 776, 779, 782, 783, 785, 791-793, 795, 796, 798-800, and 803:

SEQ ID NO: 580

L P C W I A Q V G E L C D L

SEQ ID NO: 581

L P C H M A Q L G E L C D L

SEQ ID NO: 582

H P C W M A K V G E L C D L

SEQ ID NO: 583

Y P C H M A N V G E L C D L

SEQ ID NO: 587

G R A D Q V L P C W M A Q L G E L C E L

SEQ ID NO: 590

Y P C W M A Q I G E L C D L

SEQ ID NO: 593

Y D C R F A Q L G E L C D L

SEQ ID NO: 595

T M A S N W Y D C H M A Q V G E L C D L

SEQ ID NO: 598

A Q A R F W H D C S I A H V G E L C D L

SEQ ID NO: 599

T A A E Y W Y P C W M A Q V G E L C D L

SEQ ID NO: 601

Y F C H I A K L G E L C D L

SEQ ID NO: 602

L A C R F A K L G E L C D L

SEQ ID NO: 603

L P C W M A Q L G D L C D L

SEQ ID NO: 605

K L G K G W H D C S V A Q V G E L C D L

SEQ ID NO: 606

D V F K N W Y D C R I A K L G E L C D L

SEQ ID NO: 607

E Y V L K W P D C S S A Q L G E L C E L

SEQ ID NO: 610

Y P C R M A K L G E L C D L

SEQ ID NO: 611

Y P C W L A H V G E L C D L

SEQ ID NO: 612

Y P C W M A Q L G E L C D L

SEQ ID NO: 613

Y D C S I A Q L G E L C D L

SEQ ID NO: 618

K V K L S W Y D C S V A Q V G E L C D L

SEQ ID NO: 619

G F L L E W Y D C R I A Q V G E L C D L

SEQ ID NO: 620

Y D S R S Y L P C H M A Q L G D L C D L

SEQ ID NO: 626

L P C W L A K V G D L C D L

SEQ ID NO: 627

D H L Q R W W P C R L A R L G E L C D L

SEQ ID NO: 628

K S G Q R Y Y D C S M A Q L G E L C D L

SEQ ID NO: 631

L P R S G W Y D C S I A H V G E L C D L

SEQ ID NO: 633

Y P C W I A Q V G E L C D L

SEQ ID NO: 635

L D C R F A Q V G D L C D I

SEQ ID NO: 637

Y P C W V A K L G E L C D F

SEQ ID NO: 639

L D E T Y W Y D C H V A Q V G E L C D L

SEQ ID NO: 642

R T Y D P G Q D C R L A Q L G E L C E L

SEQ ID NO: 643

L M C W L A Q L G E L C E L

SEQ ID NO: 644

Y P C W I A K V G E L C D L

SEQ ID NO: 646

Y E C H L A K L G E L C D L

SEQ ID NO: 647

R G R W E W Y D C S I A Q V G E L C D V

SEQ ID NO: 648

R S F E N W Y D C R I A Q L G E L C D L

SEQ ID NO: 654

Y P C H I A Q V G E L C D L

SEQ ID NO: 655

Y P C H V A Q L G E L C D L

SEQ ID NO: 656

Y D C S M A Q L G E L C D L

SEQ ID NO: 659

T R N E F V Y P C W L A Q V G E L C D L

SEQ ID NO: 661

E V N W L Y Y D C R F A H L G E L C D L

SEQ ID NO: 663

Y D C R I A Q V G E L C D L

SEQ ID NO: 665

F D C R F A Q V G D L C D L W S P E H I

SEQ ID NO: 666

L P C W L A N V G E L C D L P G K F E R

SEQ ID NO: 669

Y E C W M A K L G E L C D M Y L E G E I

SEQ ID NO: 674

M S W Y D C W M A Q V G E L C D L H V L

SEQ ID NO: 681

W S W Y D C R I A Q I G E L C D L I T M

SEQ ID NO: 682

W L F Y D C R W A Q V G E L C D L S G D

SEQ ID NO: 683

Y P C W I A Q I G E L C D M D P R A N M

SEQ ID NO: 684

Y D C R F A Q L G E L C D L Y E T D G R

SEQ ID NO: 692

A G W H P C H L A Q V G E L C D L D A L

SEQ ID NO: 694

Y S C G I A K V G E L C D L V D Q E P D

SEQ ID NO: 695

H P C H M A R L G E L C D L H S G V Y D

SEQ ID NO: 701

S K F Y D C R I A K L G E L C D L R S G

SEQ ID NO: 706

Y D C S I A Q L G E L C D V E P W E S M

SEQ ID NO: 710

R H F L D C R I A Q I G D L C D L I G F

SEQ ID NO: 711

P A Y Y D C S I A K V G E L C D L S M M

SEQ ID NO: 714

E Y S L D C R I A Q L G Q L C D L M R W

SEQ ID NO: 715

Y D C R M A K V G E L C D L W W D T L Y

SEQ ID NO: 716

Y D C H M A K L G E L C D L M L G D V T

SEQ ID NO: 717

Y P C H L A H V G E L C D L E G G T E F

SEQ ID NO: 718

Y D C S I A R V G E L C D L L Q D W W P

SEQ ID NO: 719

L P C W L A Q V G E L C D L Q E E T G S

SEQ ID NO: 724

G L T L P C W M A Q L G E L C D L N N A

SEQ ID NO: 725

N L H Y D C R I A Q V G E L C D L T Y E

SEQ ID NO: 728

L P C H L A Q V G E L C D L P S S M L T

SEQ ID NO: 730

T S F H D C R I A N V G E L C D L S I L

SEQ ID NO: 731

V S W Y P C H M A Q V G E L C D L G F S

SEQ ID NO: 733

A V W Y D C R I A Q V G E L C D L V H P

SEQ ID NO: 734

Y D C F F A H V G E L C D L M G N S G T

SEQ ID NO: 737

Y D C S L A Q L G E L C D L T G P S Y G

SEQ ID NO: 738

Y P C H V A Q V G E L C D L S P G L H G

SEQ ID NO: 740

S G W Y P C R I A R L G E L C D L W E G

SEQ ID NO: 741

Q V H Y D C S M A Q L G E L C D L Y D E

SEQ ID NO: 742

L W F Y D C R F A H V G E L C D L E Q T

SEQ ID NO: 747

L H I L K N Y P C Y L A Q V G E L C D L

SEQ ID NO: 748

H I M R T W Y D C S I A Q I G E L C D L

SEQ ID NO: 749

P E R G G W Y D C R F A K L G E L C D L

SEQ ID NO: 752

I S G L G I Y P C W M A H L G E L C D L

SEQ ID NO: 753

G V T Y Q W Y D C S I A L V G E L C D I

SEQ ID NO: 754

Y P C H L A L L G E L C D L

SEQ ID NO: 755

R P W R Q W Y D C S I A R L G E L C D I

SEQ ID NO: 756

Y P C W M A Q V G E L C D L

SEQ ID NO: 757

Y D C S I A K L G E L C D L

SEQ ID NO: 759

N E Q M I P W P C H L A Q L G D L C D L

SEQ ID NO: 760

F P C W L A K L G D L C D L

SEQ ID NO: 763

W S I A N F Y D C R F A H L G E L C D L

SEQ ID NO: 766

Y P C W I A K L G E L C D F

SEQ ID NO: 769

Y P C W L A R V G E L C D L D S G D V H

SEQ ID NO: 771

Y P C W M A H V G E L C D L E G W F G V

SEQ ID NO: 772

G V F Y D C R I A Q L G E L C D L W A S

SEQ ID NO: 776

H P C H M A Q V G E L C D L N F P Y V E

SEQ ID NO: 779

Y P C H M A Q L G E L C D L W S W G D I

SEQ ID NO: 782

K T W Y D C R F A Q L G E L C D L N M N

SEQ ID NO: 783

L P C W L A R L G E L C D L Q Y E Y N D

SEQ ID NO: 785

Y P C R I A K L G E L C D L S E W Q Q L

SEQ ID NO: 791

K V W Y P C R I A Q V G E L C D L D Q F

SEQ ID NO: 792

G E W Y D C R I A Q V G E L C D L W P V

SEQ ID NO: 793

Y P C W F A K L G E L C D L G L T D T K

SEQ ID NO: 795

Q F W L G C W M A Q V G E L C D L D Q P

SEQ ID NO: 796

Y T W L D C S V A Q L G Q L C D L W S M

SEQ ID NO: 798

G D L V M F Y D C R F A R V G E L C D L

SEQ ID NO: 799

R L F D P D Q N C R F A L L G E L C L L

SEQ ID NO: 800

G S V W E F Y D C F I A R V G E L C D L

SEQ ID NO: 803

Y P C W M A Q V G E L C D L F L E S V P.

23. The IL-2Rβ ligand of claim 22 , wherein the amino acid sequence is terminated with amino acids -G-G- on the N-terminus, on the C-terminus, or on both the N- and C-termini.

24. The IL-2Rβ ligand of claim 22 , wherein each amino acid sequence independently comprises from 1 to 5 of the following conservative substitutions: amino acids having a small hydrophobic side chain comprising alanine (A), glycine (G), proline (P), serine (S), or threonine (T); amino acids having a hydroxyl-containing side chain comprising serine (S), threonine (T), or tyrosine (Y); amino acids having an acidic side chain comprising aspartate (D) or glutamate (E); amino acids having a polar-neutral side chain comprising histidine (H), asparagine (N), glutamine (Q), serine (S), threonine (T), or tyrosine (Y); amino acids having a basic side chain comprising arginine (R), lysine (K), or histidine (H); amino acids having a large hydrophobic side chain comprising isoleucine (I), leucine (L), methionine (M), valine (V), phenylalanine (F), tyrosine (Y), or tryptophan (W); and amino acids having an aromatic side chain comprising phenylalanine (F), histidine (H), tryptophan (W), or tyrosine (Y).

25. The IL-2β ligand of claim 24 , wherein the IL-2Rβ ligand exhibits a binding affinity (IC 50 ) to the human IL-2Rβ subunit of less than 100 μM.

26. A pharmaceutical composition comprising the IL-2Rβ ligand of claim 22 .

27. A compound comprising at least one IL-2Rβ ligand of claim 22 .

28. The compound of claim 27 , wherein the compound is selected from a peptide comprising the IL-2Rβ ligand, a conjugate, and a fusion protein.

29. The compound of claim 27 , wherein the compound comprises an IL-2Rα ligand, an IL-2Rγc ligand, or both an IL-2Rα ligand and an IL-2Rγc ligand.

30. A pharmaceutical composition comprising the compound of claim 27 .