IL-2Rgamma binding compounds

1. An IL-2Rγc ligand comprising an amino acid sequence selected from the group consisting of:

SEQ ID NO: 954

L A L R K E V V C Q E Y Y G V E L C W I,

SEQ ID NO: 965

V V C Q D W E G V E L C W Q,

SEQ ID NO: 991

R P Q I E C Q E W Q G V E L C W T R E E,

SEQ ID NO: 1007

T D E V S C Q E W E G V E L C W I E R Q, and

SEQ ID NO: 1024

R T G V E C Q D W H G V E L C W P V W E

wherein each amino acid sequence independently comprises one 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-2Rγc ligand of claim 1 , wherein the IL-2Rγc ligand exhibits a binding affinity (IC 50 ) to the human IL-2Rγc subunit of less than 100 μM.

3. The IL-2Rγc 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 II-2Rγc ligand of claim 1 .

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

6. The compound of claim 5 , wherein the compound is selected from a polymer, an antibody, a conjugate, and a fusion protein.

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

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

9. An IL-2Rγc ligand comprising an amino acid sequence selected from the group consisting of:

SEQ ID NO: 950

I E C D T S Y G V Y I C W Q,

SEQ ID NO: 951

I E C E E W R G V E L C W Q,

SEQ ID NO: 952

P E G R E V V V C R D W Y G V E L C W Q,

SEQ ID NO: 953

I W G R T V V E C Q D W E G V E L C W Q,

SEQ ID NO: 955

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

SEQ ID NO: 956

M V N R E V V V C E D W Y G V E L C W Q,

SEQ ID NO: 957

T A N Q T V V E C Q V W G G V E L C W Q,

SEQ ID NO: 958

V E C Q E W G G V E L C W C,

SEQ ID NO: 959

D V E C V D W G G V E L C W H,

SEQ ID NO: 960

I V C E E W R G V E L C W L,

SEQ ID NO: 961

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

SEQ ID NO: 962

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

SEQ ID NO: 963

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

SEQ ID NO: 964

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

SEQ ID NO: 966

D V V C Q N W E G V D L C W H,

SEQ ID NO: 967

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

SEQ ID NO: 968

G Q G R E V V V C H D W Y G V E L C W Q,

SEQ ID NO: 969

D W R R S V V E C Q D W Y G V E L C W Q,

SEQ ID NO: 970

D V V C Q N W D G V D L C W H,

SEQ ID NO: 971

T L G R T V V E C Q D W G G V E L C W Q,

SEQ ID NO: 972

R L L N S V V E C L D W E G V E L C W Q,

SEQ ID NO: 973

I V C E D W R G V E L C W I,

SEQ ID NO: 974

V V C Q E W E G V E L C W C,

SEQ ID NO: 975

G D R P K E V V C E D W K G V E L C W I,

SEQ ID NO: 976

E R P R S F I E C Q E W E G V E L C W L,

SEQ ID NO: 977

E G S T T T I E C E E W A G V E L C W L,

SEQ ID NO: 978

A N Q N T V V E C Q D W H G V E L C W Q,

SEQ ID NO: 979

R S D D E V V V C Q E W E G V E L C W Q,

SEQ ID NO: 980

I E C E E W A G V E L C W L,

SEQ ID NO: 981

T W N M S E L E C Q D W N G V E I C W H,

SEQ ID NO: 982

G N D D S Y I V C E E W K G V E L C W I,

SEQ ID NO: 983

F A H H G V V E C Q E W Y G V E L C W Q,

SEQ ID NO: 984

L N R S V W I E C E E Y E G V E L C W L,

SEQ ID NO: 985

W S K K A E V V C E E W G G V E F C W I,

SEQ ID NO: 986

R S N Q T V V E C Q D W E G V E L C W Q,

SEQ ID NO: 987

V V C Q E W E G V E L C W Y A G E C M Q,

SEQ ID NO: 988

I L C Q E F E G V E L C W L E E S L A E,

SEQ ID NO: 989

K S Q V E C Q D W E G V E L C W V V S E,

SEQ ID NO: 990

K I T V E C Q D W D G V E L C W P T W I,

SEQ ID NO: 992

V S C Q E W D G V E L C W V D G D L A A,

SEQ ID NO: 993

I M C Q E W D G V E L C W L E R D K A N,

SEQ ID NO: 994

G L E I A C E D W Y G V E L C W L R R A,

SEQ ID NO: 995

G Y G V L C Q E W Q G V E L C W P V Q R E A G V,

SEQ ID NO: 996

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

SEQ ID NO: 997

K L T V E C Q D W D G V E L C W V G V E,

SEQ ID NO: 998

I N C Q T W N G V E L C W V D E G L Y Q,

SEQ ID NO: 999

V V C Q E W E G V E L C W V E P P L L P,

SEQ ID NO: 1000

R V Q V E C E D W N G V E L C W P V R V,

SEQ ID NO: 1001

D R Q V V C E E W D G V E L C W I E E S,

SEQ ID NO: 1002

K T T V A C Q D W G G V E L C W V E R V,

SEQ ID NO: 1003

R P E V V C Q E W E G V E L C W I S P L,

SEQ ID NO: 1004

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

SEQ ID NO: 1005

K P V V V C E E W Q G V E L C W L E I Q,

SEQ ID NO: 1006

V V C E V F Q G V E L C W C E N E E F T,

SEQ ID NO: 1008

P V E V R C Q E W E G V E L C W V V G I,

SEQ ID NO: 1009

G P E V V C E E F N R V E L C W V E Y N,

SEQ ID NO: 1010

K Y I V E C Q E W G G V E L C W P E M V,

SEQ ID NO: 1011

V T C Q E Y E G V E L C W T V G C A Y S,

SEQ ID NO: 1012

V V C Q E W E G V E L C W Q T G P G A H A,

SEQ ID NO: 1013

I V C E E Y N G V E L C W V E T S V K P,

SEQ ID NO: 1014

E Q Q V V C Q E W N G V E L C W I E A G,

SEQ ID NO: 1015

Q L G V E C Q N W R G V E L C W V S E I ,

SEQ ID NO: 1016

T A E V V C Q E W D G V E L C W I E V L,

SEQ ID NO: 1017

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

SEQ ID NO: 1018

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

SEQ ID NO: 1019

V E C E E W G G V E L C W L A D E V M W,

SEQ ID NO: 1020

H S T V I C Q D W D G V E L C W I E N D,

SEQ ID NO: 1021

K K I V V C Q D W G G V E L C W T E D D,

SEQ ID NO: 1022

S V E V V C E E W H G V E L C W P V F I,

SEQ ID NO: 1023

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

SEQ ID NO: 1025

G Y G V V C E D F R G V E L C W L E R K,

SEQ ID NO: 1026

R T E V E C E D W E G V E L C W L, and

SEQ ID NO: 1027

I L C E E W Q G V E L C W L E G G G S.

10. The IL-2Rγc ligand of claim 9 , 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.

11. The IL-2Rγc ligand of claim 9 , wherein each amino acid sequence independently comprises one 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).

12. The IL-2Rγc ligand of claim 11 , wherein the IL-2Rγc ligand exhibits a binding affinity (IC 50 ) to the human IL-2Rγc subunit of less than 100 μM.

13. A pharmaceutical composition comprising the IL-2Rγc ligand of claim 9 .

14. A compound comprising at least one IL-2Rγc ligand of claim 9 .

15. The compound of claim 14 , wherein the compound is selected from a polymer, an antibody, a conjugate, and a fusion protein.

16. The compound of claim 14 , wherein the compound further comprises an IL-2Rα ligand, an IL-2Rβ ligand, or both an IL-2Rα ligand and an IL-2Rβ ligand.

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

18. An IL-2Rγc ligand comprising the amino acid sequence of Formula (12) (SEQ ID NO: 949):

—X 171 —X 172 —X 173 —X 174 —X 175 —C—X 176 —X 177 —X 178 —X 179 —X 180 —X 181 —X 182 —X 83 —C—X 184 —X 185 —X 186 —X 187 —X 188 —  (12)

wherein,

X 171 is selected from R, K, and H;

X 172 is selected from S, T, and Y;

X 173 is selected from D, E, I, L, M, V, F, Y, and W;

X 174 is selected from I, L, M, and V;

X 175 is selected from E, I, L, M, and V;

X 176 is selected from D, E, H, and Q;

X 177 is selected from D and E;

X 178 is selected from F, W, and Y;

X 179 is selected from D, E, H, N, Q, and Y;

X 180 is selected from G;

X 181 is V;

X 182 is selected from E;

X 183 is selected from L;

X 184 is W;

X 185 is selected from I, L, V, and Y;

X 186 is E;

X 187 is selected from A, D, E, F, G, I, M, N, P, Q, R, S, T, V, W, and Y; and

X 188 is selected from D and E.

19. The IL-2Rγc ligand of claim 18 , wherein,

X 174 is selected from I and V;

X 175 is selected from E, I, L, M, and V;

X 176 is selected from D, E, and Q;

X 177 is selected from D and E;

X 17 8 is selected from F and W;

X 179 is selected from D, E, N, and Q;

X 180 is G;

X 181 is V;

X 182 is E;

X 183 is L;

X 184 is W; and

X 185 is selected from I, L, and V.

20. The IL-2Rγc ligand of claim 18 , wherein,

X 174 is V;

X 175 is selected from E, L, M, and V;

X 176 is Q;

X 177 is selected from D and E;

X 178 is W;

X 179 is selected from D, E, N, and Q;

X 180 is G;

X 181 is V;

X 182 is E;

X 183 is L;

X 184 is W; and

X 185 is selected from I, L, Q- and V.

21. The IL-2Rγc ligand of claim 18 , wherein the IL-2Rγc ligand exhibits a binding affinity (IC 50 ) to the human IL-2Rγc subunit of less than 100 μM.

22. A pharmaceutical composition comprising the IL-2Rγc ligand of claim 18 .

23. A compound comprising at least one IL-2Rγc ligand of claim 18 .

24. The compound of claim 23 , wherein the compound is selected from a polymer, an antibody, a conjugate, and a fusion protein.

25. The compound of claim 23 , wherein the compound further comprises an IL-2Rα ligand, an IL-2Rβ ligand, or both an IL-2Rα ligand and an IL-2Rβ ligand.

26. The compound of claim 23 , wherein the compound comprises a tumor-targeting moiety.

27. The compound of claim 26 , wherein the tumor-targeting moiety comprises a tumor-specific antibody, a tumor-specific antibody fragment, a tumor-specific protein, or a tumor-specific peptide.

28. The compound of claim 23 , wherein the compound comprises an immune cell-targeting moiety.

29. The compound of claim 23 , wherein the compound comprises an IgG molecule, an IgG FAb fragment, or an Fc fragment.

30. A pharmaceutical composition comprising the compound of claim 23 .