Cxcr3 ligand
AssigneeChugai Seiyaku Kabushiki Kaisha
InventorsYohei YAMAMOTO, Mika SAKURAI, Kenta HARAYA
Life of this patent
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Abstract
The present disclosure relates to CXCR3 ligands having resistance to DPPIV and having CXCR3-expressing cell migration-inducing activity, and specifically to N-terminal amino acid modifications and N-terminal amino acid sequences that are important for resistance to DPPIV and CXCR3-expressing cell migration-inducing activity.
Claims19
A CXCR3 ligand having resistance to DPPIV and having an activity to cause migration of cells expressing CXCR3.
A CXCR3 ligand having any of the following sequences (a1) to (a7) at the N-terminus:
- (a1) V-X1-L (X1 is F, G, I, K, L, M, T, V, W, or Y);
- (a2) X2-V-P (X2 is A, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, or Y);
- (a3) V-X3-P (X3 is A, F, G, H, I, K, L, M, P, Q, R, S, T, V, W, or Y);
- (a4) P-L-S;
- (a5) X4-F-P (X4 is A, D, E, F, G, H, I, K, L, M, N, P, Q, S, T, V, W, or Y);
- (a6) F-X5-M (X5 is A, D, E, G, H, I, M, N, Q, R, S, T, V, W, or Y);
- and
- (a7) F-X6-P (X6 is A, D, E, F, G, H, L, M, N, P, Q, S, T, W, or Y).
The CXCR3 ligand according to any one of claims 1 to 9, wherein the sequence of the CXCR3 ligand is any of the following (d1) to (d7):
- (d1) a sequence shown by any one of SEQ ID NOs:
- 2 to 57, 92 to 147, and 149 to 204;
- (d2) a sequence showing 90% or more sequence identity to SEQ ID NO:
- 60;
- (d3) a sequence showing 90% or more sequence identity to SEQ ID NO:
- 61;
- (d4) a sequence showing 90% or more sequence identity to SEQ ID NO:
- 62;
- (d5) a sequence showing 90% or more sequence identity to SEQ ID NO:
- 63;
- (d6) a sequence showing 90% or more sequence identity to SEQ ID NO:
- 1;
- and
- (d7) a sequence comprising 10 or less amino acid substitutions, insertions, or deletions to a sequence selected from SEQ ID NOs:
- 1 to 57, 60 to 63, 92 to 147, and 149 to 204.
A method of conferring resistance to DPPIV on a parent CXCR3 ligand in which the 2nd amino acid from the N-terminus is P or A, wherein the method comprises any of the following:
- (1) substituting the 2nd amino acid from the N-terminus of the parent CXCR3 ligand from P or A to F, G, I, K, L, M, T, V, W, or Y;
- (2) further adding A, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, or Y to the N-terminus of the parent CXCR3 ligand;
- (3) inserting A, F, G, H, I, K, L, M, P, Q, R, S, T, V, W, or Y between the 1st and 2nd amino acids at the N-terminus of the parent CXCR3 ligand;
- and
- (4) deleting V at the N-terminus of the parent CXCR3 ligand.
A method of producing a CXCR3 ligand having resistance to DPPIV, wherein the method carries out any of the following modifications to a parent CXCR3 ligand in which the 2nd amino acid from the N-terminus is P or A:
- (1) substituting the 2nd amino acid from the N-terminus of the parent CXCR3 ligand from P or A to F, G, I, K, L, M, T, V, W, or Y;
- (2) further adding A, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, or Y to the N-terminus of the parent CXCR3 ligand;
- (3) inserting A, F, G, H, I, K, L, M, P, Q, R, S, T, V, W, or Y between the 1st and 2nd amino acids at the N-terminus of the parent CXCR3 ligand;
- and
- (4) deleting the V at the N-terminus of the parent CXCR3 ligand.
A method of conferring resistance to DPPIV on a parent CXCR3 ligand in which the 2nd amino acid from the N-terminus is P, wherein the method comprises any of the following:
- (1) further adding A, D, E, F, G, H, I, K, L, M, N, P, Q, S, T, V, W, or Y to the N-terminus of the parent CXCR3 ligand;
- (2) substituting the 2nd amino acid from the N-terminus of the parent CXCR3 ligand from P to A, D, E, G, H, I, M, N, Q, R, S, T, V, W, or Y;
- and
- (3) inserting A, D, E, F, G, H, L, M, N, P, Q, S, T, W, or Y between the 1st and 2nd amino acids at the N-terminus of the parent CXCR3 ligand.
A method of producing a CXCR3 ligand having resistance to DPPIV, wherein the method carries out any of the following modifications to a parent CXCR3 ligand in which the 2nd amino acid from the N-terminus is P:
- (1) further adding A, D, E, F, G, H, I, K, L, M, N, P, Q, S, T, V, W, or Y to the N-terminus of the parent CXCR3 ligand;
- (2) substituting the 2nd amino acid from the N-terminus of the parent CXCR3 ligand from P to A, D, E, G, H, I, M, N, Q, R, S, T, V, W, or Y;
- and
- (3) inserting A, D, E, F, G, H, L, M, N, P, Q, S, T, W, or Y between the 1st and 2nd amino acids at the N-terminus of the parent CXCR3 ligand.
Dependencies are inferred from the claim text.