Abstract: A cyclic peptide is represented by Formula (I), RN-Xg-[Xi-Xa-Xm-X1-X2-X3-Xn-Xb-Xj]k-Xh-Rc - (I) in Formula (I), RN represents an N-terminal group; Rc represents a C-terminal group; X1 represents an L-leucine residue, an L-isoleucine residue, an L-methionine residue, an L-lysine residue, or an L-arginine residue; X2 represents an L-valine residue or an L-isoleucine residue; X3 represents an L-tryptophan residue or an L-phenylalanine residue; one of Xa and Xb represents an amino acid residue derived from an amino acid having an azide group on a side chain and the other represents an amino acid residue derived from an amino acid having an alkynyl group on a side chain,and Xg, Xh, X;, Xj, Xm, and Xn each represent g consecutive X"s, h consecutive X"s, i consecutive X"s, j consecutive X"s, m consecutive X"s, and n consecutive X"s; X represents an amino acid residue.
1. A cyclic peptide represented by Formula (I),
R^Xg-tXi-X^Xm-X^-X^Xn-X^XjJk-Xh-R0 - (I)
in Formula (I),
RN represents an N-terminal group;
Rc represents a C-terminal group;
X1 represents an L-leucine residue, an L-isoleucine residue, an L-methionine residue, an L-lysine residue, or an L-arginine residue;
X2 represents an L-valine residue or an L-isoleucine residue;
X3 represents an L-tryptophan residue or an L-phenylalanine residue;
one of Xa and Xb represents an amino acid residue derived from an amino acid having an azide group on a side chain and the other represents an amino acid residue derived from an amino acid having an alkynyl group on a side chain, and Xa and Xb are bonded to each other through a triazole bond;
Xg, Xh, X;, Xj, Xm, and Xn each represent g consecutive X's, h consecutive X's, i consecutive X's, j consecutive X's, m consecutive X's, and n consecutive X's;
X represents an amino acid residue, and in a case where there is a plurality of X's, the plurality of X's may be the same as or different from each other;
g, h, i, and j each independently represent an integer equal to or greater than 0;
m and n are integers satisfying 0 < m < 9, 0 < n < 9, and 3 < m + n < 9 simultaneously; and
k is an integer equal to or greater than 1, and in a case where k > 2, X1, X2, X3, Xa, Xb, X;, Xj, Xm, and Xn in a repeating unit [Xi-Xa-Xm-X1-X2-X3-Xn-Xb-Xj] each may be the same or different between the repeating units.
2. The cyclic peptide according to claim 1 that is represented by Formula (IA),
R -Xg-[XP2-X r-Xpi-X -Xm-X -X -X -Xn-X -Xqi-X S-Xq2]k-Xh-R ••• (IA)
in Formula (IA),
RN, Rc, X1, X2, X3, Xa, Xb, Xg, Xh, Xm, Xn, X, g, h, m, n, and k have the same definitions as those in Formula (I);
X4r, X5S, Xpi, Xp2, Xqi, and Xq2 each represent r consecutive X4's, s consecutive X5's, pi consecutive X's, p2 consecutive X's, ql consecutive X's, and q2 consecutive X's;
X4 and X5 each independently represent an amino acid residue derived from an amino acid having a carboxy group on a side chain or an amino acid residue derived from an amino acid having a hydroxy group on a side chain, and in a case where there is a plurality of X4's or X5's, the plurality of X4's or X5's may be the same as or different from each other;
pi, p2, ql, and q2 each independently represent an integer equal to or greater than 0;
r and s each represent an integer satisfying 0 2, X1, X2, X3, Xa, Xb, X4r, X5S, Xm, Xn, Xp2, Xpi, Xqi, and Xq2 in a repeating unit [XP2-X4r-Xpi-Xa-Xm-X1-X2-X3-Xn-Xb-Xqi-X5s-Xq2] each may be the same or different between the repeating units.
3. The cyclic peptide according to claim 1 that is represented by Formula (IB),
R -Xvi-X t-XV2-[X;-X -Xm-X -X -X -Xn-X -Xj]k-XW2-X U-Xwi-R ••• (IB)
in Formula (IB),
RN, Rc, X1, X2, X3, Xa, Xb, X;, Xj, Xm, Xn, X, i, j, m, n, and k have the same definitions as those in Formula (I);
X6t, X7U, Xvi, Xv2, Xwi, and Xw2 each represent t consecutive X6's, u consecutive X7's, vl consecutive X's, v2 consecutive X's, wl consecutive X's, and w2 consecutive X's;
X6 and X7 each independently represent an amino acid residue derived from an amino acid having an immobilizing functional group on a side chain, and in a case where there is a plurality of X6's or X7's, the plurality of X6's or X7's may be the same as or different from each other;
t and u each represent an integer satisfying 0 2, X1, X2, X3, Xa, Xb, X;, Xj, Xm, and Xn in a repeating unit [Xi-Xa-Xm-X1-X2-X3-Xn-Xb-Xj] each may be the same or different between the repeating units.
4. The cyclic peptide according to any one of claims 1 to 3 that is represented by Formula
(IC),
R -Xvi-X t-XV2-[Xp2-X r-Xpi-X -Xm-X -X -X -Xn-X -Xqi-X s-Xq2]k-XW2-X U-Xwi-R
••• (ic)
in Formula (IC),
RN, Rc, X1, X2, X3, Xa, Xb, Xm, Xn, X, m, n, and k have the same definitions as those in Formula (I);
Xpi, Xp2, Xqi, X q2, X4r, X5S, X6t, X7U, Xvi, Xv2, Xwi, and Xw2 each represent pi consecutive X's, p2 consecutive X's, ql consecutive X's, q2 consecutive X's, r consecutive X4's, s consecutive X5's, t consecutive X6's, u consecutive X7's, vl consecutive X's, v2 consecutive X's, wl consecutive X's, and w2 consecutive X's;
X4 and X5 each independently represent an amino acid residue derived from an amino acid having a carboxy group on a side chain or an amino acid residue derived from an amino acid having a hydroxy group on a side chain, and in a case where there is a plurality of X4's or X5's, the plurality of X4's or X5's may be the same as or different from each other;
X6 and X7 each independently represent an amino acid residue derived from an amino acid having an immobilizing functional group on a side chain, and in a case where there is a plurality of X6's or X7's, the plurality of X6's or X7's may be the same as or different from each other;
pi, p2, ql, and q2 each independently represent an integer equal to or greater than 0;
r and s each represent an integer satisfying 0 2, X1, X2, X3, Xa, Xb, X4r, X5S, Xm, Xn, Xp2, Xpi, Xqi, and Xq2 in a repeating unit [XP2-X4r-Xpi-Xa-Xm-X1-X2-X3-Xn-Xb-Xqi-X5s-Xq2] each may be the same or different between the repeating units.
5. The cyclic peptide according to claim 2 or 4,
wherein the amino acid having a carboxy group on a side chain is at least one of amino acid selected from the group consisting of L-aspartic acid, D-aspartic acid, L-glutamic
acid, D-glutamic acid, L-homoglutamic acid, and D-homoglutamic acid, and the amino acid having a hydroxy group on a side chain is at least one of amino acid selected from the group consisting of L-serine, D-serine, L-homoserine, D-homoserine, L-tyrosine, D-tyrosine, L-threonine, D-threonine, L-allothreonine, and D-allothreonine.
6. The cyclic peptide according to claim 3 or 4,
wherein the amino acid having an immobilizing functional group on a side chain is at least one of amino acid selected from the group consisting of L-lysine, D-lysine, L-cysteine, D-cysteine, L-homocysteine, and D-homocysteine.
7. The cyclic peptide according to any one of claims 1 to 6,
wherein the amino acid having an azide group on a side chain is at least one of amino acid selected from the group consisting of P-azide-L-alanine, y-azide-L-homoalanine, 8-azide-L-norvaline, and s-azide-L-lysine, and the amino acid having an alkynyl group on a side chain is at least one of amino acid selected from the group consisting of L-propargylglycine, L-homopropargylglycine, and L-bishomopropargylglycine.
8. The cyclic peptide according to any one of claims 1 to 7,
wherein Xm-X^X^X3-^ and an amino acid sequence (SEQ ID NO: 1) represented by Formula (1) or an amino acid sequence (SEQ ID NO: 2) represented by Formula (2) share sequence homology equal to or higher than 70%,
A-Y-H-L^G-E-L^V-W ••• (1)
A-Y-H-R-G-E-L2-V-W ••• (2)
in Formula (1) and Formula (2),
A represents an L-alanine residue or a D-alanine residue;
Y represents an L-tyrosine residue or a D-tyrosine residue;
H represents an L-histidine residue or a D-histidine residue;
L1 represents an L-leucine residue or a D-leucine residue;
R represents an L-arginine residue or a D-arginine residue;
G represents a glycine residue;
E represents an L-glutamic acid residue or a D-glutamic acid residue; L2 represents an L-leucine residue;
V represents an L-valine residue; and
W represents an L-tryptophan residue.
9. The cyclic peptide according to any one of claims 1 to 8,
wherein k = 1.
10. The cyclic peptide according to claim 1 that is represented by Formula (II),
R -Xvo-X to-Xeo-X ro-Xpo-X -A-Y-H-X -G-E-L-V-W-X -Xqo-X so-Xfo-X uo-Xwo-R
(II)
in Formula (II),
Xa, Xb, X, RN, and Rc have the same definitions as those in Formula (I);
X4 and X5 each independently represent an L-amino acid residue or a D-amino acid residue having a carboxy group or a hydroxy group on a side chain, and in a case where there is a plurality of X4's or X5's, the plurality of X4's or X5's may be the same as or different from each other;
X6 and X7 each independently represent an L-amino acid residue or a D-amino acid residue having an immobilizing functional group on a side chain, and in a case where there is a plurality of X6's or X7's, the plurality of X6's or X7's may be the same as or different from each other;
X8 represents any one residue selected from the group consisting of an L-leucine residue, an L-arginine residue, a D-leucine residue, and a D-arginine residue;
eO and fO each represent an integer satisfying 0 < eO < 10 and 0 < f0 < 10;
pO and qO each represent an integer satisfying 0 < pO < 5 and 0 < qO < 5;
rO and sO each represent an integer satisfying 0 < rO < 5 and 0 < sO < 5;
tO and uO each represent an integer satisfying 0 < tO < 5 and 0 < uO < 5;
vO and wO each represent an integer satisfying 0 < vO < 5 and 3 < wO < 5;
pO, qO, rO, sO, tO, uO, vO, and wO satisfy 0 < pO + qO + rO + sO + tO + uO + vO + wO < 39;
A represents an L-alanine residue or a D-alanine residue;
Y represents an L-tyrosine residue or a D-tyrosine residue;
H represents an L-histidine residue or a D-histidine residue;
G represents a glycine residue;
E represents an L-glutamic acid residue or a D-glutamic acid residue;
L represents an L-leucine residue;
V represents an L-valine residue; and W represents an L-tryptophan residue.
11. The cyclic peptide according to any one of claims 1 to 10 that is an antibody binding ligand.
12. The cyclic peptide according to any one of claims 1 to 10 that is a linker for labeling antibodies.
13. The cyclic peptide according to any one of claims 1 to 10 that is a linker for antibody drug conjugates.
14. The cyclic peptide according to any one of claims 1 to 10 that is a drug carrier.
15. An affinity chromatography support comprising:
a water insoluble carrier; and
the cyclic peptide according to any one of claims 1 to 10,
wherein the water insoluble carrier and the cyclic peptide are directly or indirectly bonded to each other.
16. A labeled antibody comprising:
an antibody;
a labeling compound; and
the cyclic peptide according to any one of claims 1 to 10,
wherein the antibody and the labeling compound are bonded to each other through the cyclic peptide.
17. An antibody drug conjugate comprising:
an antibody; a drug; and
the cyclic peptide according to any one of claims 1 to 10,
wherein the antibody and the drug are bonded to each other through the cyclic peptide.
18. The antibody drug conjugate according to claim 17,
wherein the drug is a drug having undergone liposomization, polymer micellization, or PEGylation.
19. A pharmaceutical preparation comprising:
a drug; and
the cyclic peptide according to any one of claims 1 to 10,
wherein the drug and the cyclic peptide are directly or indirectly bonded to each other.
20. The pharmaceutical preparation according to claim 19,
wherein the drug is a drug having undergone liposomization, polymer micellization, or PEGylation.
| # | Name | Date |
|---|---|---|
| 1 | 201947010403.pdf | 2019-03-18 |
| 2 | 201947010403-TRANSLATIOIN OF PRIOIRTY DOCUMENTS ETC. [18-03-2019(online)].pdf | 2019-03-18 |
| 3 | 201947010403-STATEMENT OF UNDERTAKING (FORM 3) [18-03-2019(online)].pdf | 2019-03-18 |
| 4 | 201947010403-SEQUENCE LISTING(PDF) [18-03-2019(online)].pdf | 2019-03-18 |
| 5 | 201947010403-SEQUENCE LISTING [18-03-2019(online)].txt | 2019-03-18 |
| 6 | 201947010403-REQUEST FOR EXAMINATION (FORM-18) [18-03-2019(online)].pdf | 2019-03-18 |
| 7 | 201947010403-PROOF OF RIGHT [18-03-2019(online)].pdf | 2019-03-18 |
| 8 | 201947010403-PRIORITY DOCUMENTS [18-03-2019(online)].pdf | 2019-03-18 |
| 9 | 201947010403-POWER OF AUTHORITY [18-03-2019(online)].pdf | 2019-03-18 |
| 10 | 201947010403-FORM 18 [18-03-2019(online)].pdf | 2019-03-18 |
| 11 | 201947010403-FORM 1 [18-03-2019(online)].pdf | 2019-03-18 |
| 12 | 201947010403-DECLARATION OF INVENTORSHIP (FORM 5) [18-03-2019(online)].pdf | 2019-03-18 |
| 13 | 201947010403-COMPLETE SPECIFICATION [18-03-2019(online)].pdf | 2019-03-18 |
| 14 | 201947010403-CLAIMS UNDER RULE 1 (PROVISIO) OF RULE 20 [18-03-2019(online)].pdf | 2019-03-18 |
| 15 | Correspondence by Agent_Form1 _20-03-2019.pdf | 2019-03-20 |
| 16 | 201947010403-FORM 3 [04-06-2019(online)].pdf | 2019-06-04 |
| 17 | 201947010403-OTHERS [29-07-2021(online)].pdf | 2021-07-29 |
| 18 | 201947010403-MARKED COPIES OF AMENDEMENTS [29-07-2021(online)].pdf | 2021-07-29 |
| 19 | 201947010403-FORM-26 [29-07-2021(online)].pdf | 2021-07-29 |
| 20 | 201947010403-FORM 3 [29-07-2021(online)].pdf | 2021-07-29 |
| 21 | 201947010403-FORM 13 [29-07-2021(online)].pdf | 2021-07-29 |
| 22 | 201947010403-FER_SER_REPLY [29-07-2021(online)].pdf | 2021-07-29 |
| 23 | 201947010403-CLAIMS [29-07-2021(online)].pdf | 2021-07-29 |
| 24 | 201947010403-AMMENDED DOCUMENTS [29-07-2021(online)].pdf | 2021-07-29 |
| 25 | 201947010403-ABSTRACT [29-07-2021(online)].pdf | 2021-07-29 |
| 26 | 201947010403-PatentCertificate12-10-2021.pdf | 2021-10-12 |
| 27 | 201947010403-IntimationOfGrant12-10-2021.pdf | 2021-10-12 |
| 28 | 201947010403-FER.pdf | 2021-10-17 |
| 29 | 201947010403-RELEVANT DOCUMENTS [16-09-2023(online)].pdf | 2023-09-16 |
| 1 | 201947010403SSE_06-08-2020.pdf |