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Peptide Compound And Method For Producing Same, Composition For Screenint Use, And Method For Selecting Peptide Compound

Abstract: The present invention addresses the problem of providing a novel cyclic peptide compound excellent in cell membrane permeability a method for producing the same a composition for screening use and a method for selecting a cyclic peptide compound that couples to a target substance. According to the present invention a peptide compound represented by formula (1) or a salt thereof is provided. In the formula the symbols have the meanings as defined in the specification of the present application.

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Patent Information

Application #
Filing Date
01 October 2019
Publication Number
41/2019
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
patent@depenning.com
Parent Application

Applicants

FUJIFILM CORPORATION
26-30, Nishiazabu 2-chome, Minato-ku, Tokyo 1068620

Inventors

1. INOUE Masaaki
c/o FUJIFILM CORPORATION, 577, Ushijima, Kaisei-machi, Ashigarakami-gun, Kanagawa 2588577
2. TAMURA Takashi
c/o FUJIFILM CORPORATION, 577, Ushijima, Kaisei-machi, Ashigarakami-gun, Kanagawa 2588577
3. YOSHIMITSU Yuji
c/o FUJIFILM CORPORATION, 577, Ushijima, Kaisei-machi, Ashigarakami-gun, Kanagawa 2588577
4. HOHSAKA Takahiro
c/o JAPAN ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY, 1-1, Asahidai, Nomi-shi, Ishikawa 9231292
5. WATANABE Takayoshi
c/o JAPAN ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY, 1-1, Asahidai, Nomi-shi, Ishikawa 9231292

Specification

A peptide compound represented by Formula (1) or a salt thereof:
in the formula,
X represents S, NH, or O;
A represents a single bond, or a linear alkylene group having 1 or 2 carbon atoms which may have a substituent;
B represents a single bond or a linear alkylene group having 1 or 2 carbon atoms which may have a substituent, provided that A and B are not simultaneously a single bond;
Z represents a hydroxyl group or an amino group;
p pieces of R's may be the same as or different from one another and each represent a heteroarylene group which may have a substituent or an arylene group having 6 to 10 carbon atoms which may have a substituent;
G represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms which may have a substituent in a case where the carbon to which G is bonded together with A does not form a divalent group represented by *-CR°=C(B)-;
t1 pieces of W1 s may be the same as or different from one another and each represent a single bond, -CH2(C6HsNH)-, -CH2(C6HsO)-, an amino acid residue which may have a substituent, a heteroarylene group which may have a substituent, an arylene group having 6 to 20 carbon atoms which may have a substituent, or an alkylene group having 1 to 6 carbon atoms which may have a substituent;
t2 pieces of W2's may be the same as or different from one another and each represent a single bond, -CO-, -COO-, -NHCO-, -NHCONH-, -CONHCO-, -(CH2CH20)-, -(CH2CH2CH2O)-, an amino acid residue which may have a substituent, a heteroarylene group which may have a substituent, an arylene group having 6 to 20 carbon atoms which may have a substituent, or an alkylene group having 1 to 6 carbon atoms which may have a substituent;
J represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms which may have a substituent;

n pieces of Xaa's each independently represent any amino acid residue or any amino acid analog residue;
m pieces of Xbb's each independently represent any amino acid residue or any amino acid analog residue;
p represents an integer of 0 to 4;
t1 represents an integer of 0 to 6;
t represents an integer of 0 to 6;
m represents an integer of 0 to 20; and
n represents an integer of 1 to 20.
2. A peptide compound represented by Formula (1 A) or a salt thereof:
in the formula,
A1 represents a linear alkylene group having 1 or 2 carbon atoms which may have a substituent;
p1 pieces of R/'s may be the same as or different from one another and each represent a heteroarylene group which may have a substituent or an arylene group having 6 to 10 carbon atoms which may have a substituent;
t11 pieces of Wn's may be the same as or different from one another and each represent a single bond, -CH2(C6H5NH)-, -CH2(C6H50)-, an amino acid residue which may have a substituent, a heteroarylene group which may have a substituent, an arylene group having 6 to 20 carbon atoms which may have a substituent, or an alkylene group having 1 to 6 carbon atoms which may have a substituent;
0 1 0 1
t pieces of W 's may be the same as or different from one another and each represent a single bond, -CO-, -COO-, -NHCO-, -NHCONH-, -CONHCO-, -(CH2CH20)-, -(CH2CH2CH20)-, an amino acid residue which may have a substituent, a heteroarylene group which may have a substituent, an arylene group having 6 to 20 carbon atoms which may have a substituent, or an alkylene group having 1 to 6 carbon atoms which may have a substituent;

G1 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms which may have a substituent in a case where the carbon to which G1 is bonded together with A1 does not form a divalent group represented by *-CH=C(N)-;
J1 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms which may have a substituent;
p1 represents an integer of 0 to 4;
t11 represents an integer of 0 to 6;
t21 represents an integer of 0 to 6; and
Z, Xaa, Xbb, m, and n have the same meaning as the definition in claim 1.
3. A peptide compound represented by Formula (IB) or a salt thereof:
in the formula,
A represents a linear alkylene group having 1 or 2 carbon atoms which may have a substituent, or a divalent group represented by *-CH=C(N)- together with the carbon atom to which N is bonded, in which * represents a position that is bonded to S;
G2 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms which may have a substituent in a case where the carbon to which G2 is bonded together with A does not form a divalent group represented by *-CH=C(N)-;
J represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms which may have a substituent;
p2 pieces of R2's may be the same as or different from one another and each represent a heteroarylene group which may have a substituent or an arylene group having 6 to 10 carbon atoms which may have a substituent;
p represents an integer of 0 to 4;
q2 represents an integer of 0 to 6, provide that p2 and q2 are not simultaneously 0; and
Z, Xaa, Xbb, m, and n have the same meaning as the definition in claim 1.

4. The peptide compound or the salt thereof according to any one of claims 1 to 3, wherein the R, R , or R is at least one structure selected from a benzothiazolylene group which may have a substituent, a benzooxazolylene group which may have a substituent, a benzoimidazolylene group which may have a substituent, a benzothiophenylene group which may have a substituent, a benzofuranylene group which may have a substituent, an isobenzofuranylene group which may have a substituent, an indolylene group which may have a substituent, a quinolylene group which may have a substituent, an isoquinolylene group which may have a substituent, a quinazolylene group which may have a substituent, a cinnolylene group which may have a substituent, an indazolylene group which may have a substituent, a benzothiadiazolylene group which may have a substituent, a pyridinylene group which may have a substituent, a pyridazinylene group which may have a substituent, a pyrimidinylene group which may have a substituent, a pyrazinylene group which may have a substituent, a thiazolylene group which may have a substituent, an imidazolylene group which may have a substituent, an oxazolylene group which may have a substituent, an oxadiazolylene group which may have a substituent, a thiadiazolylene group which may have a substituent, a pyrazolylene group which may have a substituent, an isoxazolylene group which may have a substituent, a triazolylene group which may have a substituent, an imidazothiazolylene group which may have a substituent, an imidazopyridinylene group which may have a substituent, an imidazopyridazinylene group which may have a substituent, an imidazopyrimidinylene group which may have a substituent, an imidazopyrazinylene group which may have a substituent, a pyrazolopyrimidinylene group which may have a substituent, a pyrrolopyridinylene group which may have a substituent, a thiophenylene group which may have a substituent, a furanylene group which may have a substituent, a pyrrolene group which may have a substituent, a phenylene group which may have a substituent, and a naphthylene group which may have a substituent.
5. The peptide compound or the salt thereof according to any one of claims 1 to 4, wherein R, R , or R is at least one structure selected from a benzothiophenylene group which may have a substituent, an indolylene group which may have a substituent, a quinolylene group which may have a substituent, an indazolylene group which may have a substituent, a pyrrolopyridinylene group which may have a substituent, an imidazopyrazinylene group which may have a substituent, a pyridinylene group which may have a substituent, a pyridazinylene group which may have a substituent, a pyrazinylene group which may have a substituent, a thiazolylene group which may have a substituent, an oxazolylene group which may have a substituent, a triazolylene group which may have a substituent, a thiophenylene group which may have a substituent, and a phenylene group which may have a substituent.

6. The peptide compound or the salt thereof according to any one of claims 1 to 5, wherein the total number of amino acid residues and amino acid analog residues constituting a cyclic portion of the peptide compound is 3 to 20.
7. The peptide compound or the salt thereof according to any one of claims 1 to 6, wherein the total number of amino acid residues and amino acid analog residues constituting the peptide compound is 3 to 20.
8. The peptide compound or the salt thereof according to any one of claims 1 to 7, wherein Xaa is a-amino acid residue.
9. The peptide compound or the salt thereof according to any one of claims 1 to 8, wherein Xaa comprises a natural amino acid residue.

10. The peptide compound or the salt thereof according to any one of claims 1 to 9, wherein p, pi or p is 1.
11. A composition for screening use, comprising:
the peptide compound or the salt thereof according to any one of claims 1 to 10.
12. A method for selecting a peptide compound or a salt thereof that binds to a target
substance, comprising:
bringing a target substance into contact with a peptide library containing the peptide compound or the salt thereof according to any one of claims 1 to 10 to select a peptide compound or a salt thereof that binds to the target substance.
13. A method for producing a peptide compound or a salt thereof, comprising;
a step of producing a peptide chain having an amino acid residue or amino acid analog residue having a cyano group in the side chain in the peptide chain or at the C-terminus and having a structure of Formula (2) at the N-terminus; and
a step of reacting the cyano group with the structure of Formula (2) to form a cyclic portion having a bond represented by Formula (3):

X represents S, NH, or O;
A represents a single bond or a linear alkylene group having 1 or 2 carbon atoms which may have a substituent;
B represents a single bond or a linear alkylene group having 1 or 2 carbon atoms which may have a substituent;
G represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms which may have a substituent;
* represents a bonding site to a peptide chain; and
A and B are not simultaneously a single bond;
X, A, G, and B have the same meaning as the definition in Formula (2).
14. A method for selecting a peptide compound that binds to a target substance,
comprising:
a step of producing a peptide compound having a cyclic portion by the method according to claim 13; and
a step of bringing a target substance into contact with a peptide library containing the peptide compound or the salt thereof to select a peptide compound or a salt thereof that binds to the target substance.
15. The selection method according to claim 14, comprising the following steps:
(i) a step of preparing a nucleic acid library, carrying out translation by a cell-free translation system containing an elongating tRNA acylated with an unnatural amino acid, and preparing a library containing a peptide compound in which the unnatural amino acid is randomly incorporated into a peptide sequence;
(ii) a step of bringing the peptide library into contact with a target substance; and
(iii) a step of selecting a peptide compound that binds to the target substance,
in the step (i), each peptide compound constituting the library is translated from the nucleic acid sequence encoding each peptide compound constituting the library, and the nucleic acid sequence and the peptide as the translation product thereof are linked to construct an in vitro display library, and
the step (iii) includes determining a nucleic acid sequence encoding a peptide compound that binds to a target substance, determining a peptide sequence from the nucleic acid sequence, and selecting a peptide compound.

16. The method according to any one of claims 13 to 15, wherein the amino acid residue and/or the amino acid analog residue having the cyano group in the side chain is a structure represented by Formula (4):
in the formula,
m1 pieces of Q^s may be the same as or different from one another and represent at least one of a heteroarylene group which may have a substituent, an arylene group having 6 to 10 carbon atoms which may have a substituent, or an alkylene group having 1 to 6 carbon atoms which may have a substituent;
T1 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms which may have a substituent;
n1 represents an integer of 0 to 6, and m1 represents an integer of 1 to 4; and
* represents a binding position to the amino acid residue and/or amino acid analog residue constituting the peptide chain.
17. The method according to any one of claims 13 to 15, wherein the amino acid residue and/or the amino acid analog residue having the cyano group in the side chain is a structure represented by Formula (5):
in the formula,
l2 pieces of Q2's may be the same as or different from one another and each represent a single bond, -CH2(C6HsNH)-, -CH2(C6HsO)-, an amino acid residue which may have a substituent, a heteroarylene group which may have a substituent, an

arylene group having 6 to 20 carbon atoms which may have a substituent, or an alkylene group having 1 to 6 carbon atoms which may have a substituent;
9 ^
n pieces of Q 's may be the same as or different from one another and each represent a single bond, -CO-, -COO-, -NHCO-, -NHCONH-, -CONHCO-, -(CH2CH20)-, -(CH2CH2CH20)-, an amino acid residue which may have a substituent, a heteroarylene group which may have a substituent, an arylene group having 6 to 20 carbon atoms which may have a substituent, or an alkylene group having 1 to 6 carbon atoms which may have a substituent;
9 4
m pieces of Q 's may be the same as or different from one another and represent at least one of a heteroarylene group which may have a substituent, an arylene group having 6 to 10 carbon atoms which may have a substituent, or an alkylene group having 1 to 6 carbon atoms which may have a substituent;
T represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms which may have a substituent;
1 represents an integer of 0 to 6;
n represents an integer of 0 to 6;
m represents an integer of 1 to 4; and
* represents a binding position with the amino acid residue and/or amino acid analog residue constituting the peptide chain.
18. The method according to claim 16 or 17, wherein the Q1 or Q4 is at least one structure selected from a benzothiazolylene group which may have a substituent, a benzooxazolylene group which may have a substituent, a benzoimidazolylene group which may have a substituent, a benzothiophenylene group which may have a substituent, a benzofuranylene group which may have a substituent, an isobenzofuranylene group which may have a substituent, an indolylene group which may have a substituent, a quinolylene group which may have a substituent, an isoquinolylene group which may have a substituent, a quinazolylene group which may have a substituent, a cinnolylene group which may have a substituent, an indazolylene group which may have a substituent, a benzothiadiazolylene group which may have a substituent, a pyridinylene group which may have a substituent, a pyridazinylene group which may have a substituent, a pyrimidinylene group which may have a substituent, a pyrazinylene group which may have a substituent, a thiazolylene group which may have a substituent, an imidazolylene group which may have a substituent, an oxazolylene group which may have a substituent, an oxadiazolylene group which may have a substituent, a thiadiazolylene group which may have a substituent, a pyrazolylene group which may have a substituent, an isoxazolylene group which may have a substituent, a triazolylene group which may have a substituent, an imidazothiazolylene group which may have a substituent, an imidazopyridinylene group which may have a substituent, an imidazopyridazinylene group which may have

a substituent, an imidazopyrimidinylene group which may have a substituent, an imidazopyrazinylene group which may have a substituent, a pyrazolopyrimidinylene group which may have a substituent, a pyrrolopyridinylene group which may have a substituent, a thiophenylene group which may have a substituent, a furanylene group which may have a substituent, a pyrrolene group which may have a substituent, a phenylene group which may have a substituent, and a naphthylene group which may have a substituent.
19. The method according to any one of claims 16 to 18, wherein the Q1 or Q4 is at least one structure selected from a benzothiophenylene group which may have a substituent, an indolylene group which may have a substituent, a quinolylene group which may have a substituent, an indazolylene group which may have a substituent, a pyrrolopyridinylene group which may have a substituent, an imidazopyrazinylene group which may have a substituent, a pyridinylene group which may have a substituent, a pyridazinylene group which may have a substituent, a pyrazinylene group which may have a substituent, a thiazolylene group which may have a substituent, an oxazolylene group which may have a substituent, a triazolylene group which may have a substituent, a thiophenylene group which may have a substituent, and a phenylene group which may have a substituent.
20. The method according to any one of claims 13 to 19, wherein Formula (2) is a structure represented by Formula (2A):
in the formula,
A1 represents a linear alkylene group having 1 or 2 carbon atoms which may have a substituent; and
G represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms which may have a substituent.
21. The method according to any one of claims 13 to 20, wherein Formula (2) is at least one structure selected from the following formulae.

22. The method according to any one of claims 13 to 21, wherein a reaction solvent in the step of reacting the cyano group with the structure of Formula (2) to form a bond represented by Formula (3) is water.
23. The method according to any one of claims 13 to 22, wherein a pH of a reaction solution in the step of reacting the cyano group with the structure of Formula (2) to form the bond represented by Formula (3) is 6.0 to 8.5.
24. The method according to any one of claims 13 to 23, wherein the total number of amino acid residues and amino acid analog residues constituting the cyclic portion of the peptide compound having a cyclic portion is 3 to 20.
25. The method according to any one of claims 13 to 24, wherein the total number of amino acid residues and amino acid analog residues constituting the peptide compound having a cyclic portion is 3 to 20.
26. The method according to any one of claims 13 to 25, wherein the amino acid residues or amino acid analog residues having a heteroarylene group having a cyano group, an arylene group having a cyano group, or an alkylene group having a cyano group in the side chain are incorporated into the peptide chain using codons that become empty codons by excluding natural amino acids from codons assigned in the translation of natural amino acids, stop codons, or four-base codons.
27. A composition for screening use, comprising a peptide compound having a cyclic portion or a salt thereof, wherein the cyclic portion has a structure represented by Formula (6):

A represents a single bond, or a linear alkylene group having 1 or 2 carbon atoms which may have a substituent;
B represents a single bond or a linear alkylene group having 1 or 2 carbon atoms which may have a substituent, provided that A and B are not simultaneously a single bond;
p pieces of R's may be the same as or different from one another and each represent a heteroarylene group which may have a substituent or an arylene group having 6 to 10 carbon atoms which may have a substituent;
G represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms which may have a substituent in a case where the carbon to which G is bonded together with A does not form a divalent group represented by *-CR°=C(B)-; and
p represents an integer of 0 to 4.

Documents

Orders

Section Controller Decision Date

Application Documents

# Name Date
1 201947039670-US(14)-HearingNotice-(HearingDate-26-07-2021).pdf 2021-10-18
1 201947039670.pdf 2019-10-01
2 201947039670-Correspondence to notify the Controller [22-07-2021(online)].pdf 2021-07-22
2 201947039670-TRANSLATIOIN OF PRIOIRTY DOCUMENTS ETC. [01-10-2019(online)].pdf 2019-10-01
3 201947039670-STATEMENT OF UNDERTAKING (FORM 3) [01-10-2019(online)].pdf 2019-10-01
3 201947039670-CLAIMS [29-05-2020(online)].pdf 2020-05-29
4 201947039670-SEQUENCE LISTING(PDF) [01-10-2019(online)].pdf 2019-10-01
4 201947039670-FER_SER_REPLY [29-05-2020(online)].pdf 2020-05-29
5 201947039670-SEQUENCE LISTING [01-10-2019(online)].txt 2019-10-01
5 201947039670-FORM 3 [29-05-2020(online)].pdf 2020-05-29
6 201947039670-REQUEST FOR EXAMINATION (FORM-18) [01-10-2019(online)].pdf 2019-10-01
6 201947039670-Information under section 8(2) [29-05-2020(online)].pdf 2020-05-29
7 201947039670-PROOF OF RIGHT [01-10-2019(online)].pdf 2019-10-01
7 201947039670-OTHERS [29-05-2020(online)].pdf 2020-05-29
8 201947039670-PRIORITY DOCUMENTS [01-10-2019(online)].pdf 2019-10-01
8 201947039670-FORM 3 [19-02-2020(online)].pdf 2020-02-19
9 201947039670-FER.pdf 2020-02-12
9 201947039670-FORM 18 [01-10-2019(online)].pdf 2019-10-01
10 201947039670-certified copy of translation (MANDATORY) [12-12-2019(online)].pdf 2019-12-12
10 201947039670-FORM 1 [01-10-2019(online)].pdf 2019-10-01
11 201947039670-DECLARATION OF INVENTORSHIP (FORM 5) [01-10-2019(online)].pdf 2019-10-01
11 201947039670-FORM 3 [11-12-2019(online)].pdf 2019-12-11
12 201947039670-COMPLETE SPECIFICATION [01-10-2019(online)].pdf 2019-10-01
12 201947039670-FORM-26 [11-10-2019(online)].pdf 2019-10-11
13 201947039670-CLAIMS UNDER RULE 1 (PROVISIO) OF RULE 20 [01-10-2019(online)].pdf 2019-10-01
13 Correspondence by Agent_Form-1 And Power of Attorney_11-10-2019.pdf 2019-10-11
14 201947039670-CLAIMS UNDER RULE 1 (PROVISIO) OF RULE 20 [01-10-2019(online)].pdf 2019-10-01
14 Correspondence by Agent_Form-1 And Power of Attorney_11-10-2019.pdf 2019-10-11
15 201947039670-COMPLETE SPECIFICATION [01-10-2019(online)].pdf 2019-10-01
15 201947039670-FORM-26 [11-10-2019(online)].pdf 2019-10-11
16 201947039670-DECLARATION OF INVENTORSHIP (FORM 5) [01-10-2019(online)].pdf 2019-10-01
16 201947039670-FORM 3 [11-12-2019(online)].pdf 2019-12-11
17 201947039670-FORM 1 [01-10-2019(online)].pdf 2019-10-01
17 201947039670-certified copy of translation (MANDATORY) [12-12-2019(online)].pdf 2019-12-12
18 201947039670-FER.pdf 2020-02-12
18 201947039670-FORM 18 [01-10-2019(online)].pdf 2019-10-01
19 201947039670-FORM 3 [19-02-2020(online)].pdf 2020-02-19
19 201947039670-PRIORITY DOCUMENTS [01-10-2019(online)].pdf 2019-10-01
20 201947039670-OTHERS [29-05-2020(online)].pdf 2020-05-29
20 201947039670-PROOF OF RIGHT [01-10-2019(online)].pdf 2019-10-01
21 201947039670-Information under section 8(2) [29-05-2020(online)].pdf 2020-05-29
21 201947039670-REQUEST FOR EXAMINATION (FORM-18) [01-10-2019(online)].pdf 2019-10-01
22 201947039670-FORM 3 [29-05-2020(online)].pdf 2020-05-29
22 201947039670-SEQUENCE LISTING [01-10-2019(online)].txt 2019-10-01
23 201947039670-FER_SER_REPLY [29-05-2020(online)].pdf 2020-05-29
23 201947039670-SEQUENCE LISTING(PDF) [01-10-2019(online)].pdf 2019-10-01
24 201947039670-CLAIMS [29-05-2020(online)].pdf 2020-05-29
24 201947039670-STATEMENT OF UNDERTAKING (FORM 3) [01-10-2019(online)].pdf 2019-10-01
25 201947039670-TRANSLATIOIN OF PRIOIRTY DOCUMENTS ETC. [01-10-2019(online)].pdf 2019-10-01
25 201947039670-Correspondence to notify the Controller [22-07-2021(online)].pdf 2021-07-22
26 201947039670.pdf 2019-10-01
26 201947039670-US(14)-HearingNotice-(HearingDate-26-07-2021).pdf 2021-10-18

Search Strategy

1 search_11-02-2020.pdf