Method of improving blood kinetics of peptide
A method for improving blood kinetics of a peptide is provided. The method for improving blood kinetics of a peptide includes a step of preparing a peptide having a modified amino acid sequence.
1 . A conjugate of a peptide comprising, from the amino terminus to the carboxyl terminus, two or three aspartic acids and/or glutamic acids, the amino acid sequence of a SPINK2 variant peptide set forth in SEQ ID NO: 2, and an amino acid sequence comprising an Fc region of human IgG1, IgG2, or IgG4P, in this order, wherein the Fc region is represented by any one of the amino acid sequences set forth in SEQ ID NO: 34, 37, or 40, and
wherein the conjugate has a suppressed blood concentration decrease over time or an increased blood exposure amount compared to a conjugate lacking the two or three aspartic acids and/or glutamic acids at the amino terminus.
2 . The conjugate according to claim 1 , wherein the amino acid sequence of the SPINK2 variant peptide is attached via a linker sequence to the amino acid sequence comprising the Fc region.
3 . The conjugate according to claim 1 , wherein the amino acid sequence of the SPINK2 variant peptide is directly attached to the amino acid sequence comprising the Fc region.
4 . The conjugate according to claim 1 , wherein the two or three aspartic acids and/or glutamic acids are attached via a linker sequence to the amino acid sequence of the SPINK2 variant peptide.
5 . The conjugate according to claim 1 , wherein the two or three aspartic acids and/or glutamic acids are directly attached to the amino acid sequence of the SPINK2 variant peptide.
6 . The conjugate according to claim 1 , wherein the SPINK2 variant peptide binds to a human disease-related target molecule.
7 . A composition comprising the conjugate according to claim 1 .
8 . The conjugate according to claim 1 , wherein the SPINK2 variant peptide suppresses, inhibits, agonizes or activates an activity of a human disease-related target molecule.
9 . A pharmaceutical composition comprising the conjugate according to claim 8 .
10 . A method for producing the conjugate according to claim 1 , comprising step (i) or (ii):
(i) adding the two or three aspartic acids and/or glutamic acids to the amino terminus end of a fusion containing the SPINK2 variant peptide and the Fc region; or
(ii) introducing, into a cell, a polynucleotide encoding an amino acid sequence (c) containing an amino acid sequence (a) contained in the fusion and an amino acid sequence (b) consisting of the two or three aspartic acids and/or glutamic acids, wherein the amino acid sequence (b) is located at the amino terminus end of the amino acid sequence (a), culturing the cell, and recovering a conjugate containing the fusion from the culture.
11 . The method according to claim 10 , wherein the Fc region is fused via a linker to the SPINK2 variant peptide, or an amino acid sequence contained in the SPINK2 variant peptide is attached via a linker sequence to an amino acid sequence contained in the Fc region.
12 . The method according to claim 10 , wherein the two or three aspartic acids and/or glutamic acids are attached via a linker to the amino terminus end of the fusion.
13 . The method according to claim 10 , wherein the two or three aspartic acids and/or glutamic acids are directly attached to the amino terminus end of the fusion.