SOLID-PHASE CARRIER, PRODUCTION METHOD FOR SOLID-PHASE CARRIER, CARRIER FOR AFFINITY REFINING, PRODUCTION METHOD FOR FILLER FOR AFFINITY CHROMATOGRAPHY, FILLER FOR AFFINITY CHROMATOGRAPHY, CHROMATOGRAPHY COLUMN, AND REFINING METHOD
There are provided a solid-phase carrier and a carrier for affinity refining that exhibit high dynamic binding capacity when a ligand is immobilized, have excellent antifouling properties, and are unlikely to have non-specific adsorption of impurities. The solid-phase carrier has a functional group capable of fixing a ligand and is characterized by having a group having a sulfinyl group, a sulfide group, an oxy group or an imino group, and a hydroxyl group, a thiol group, an amino group, a carboxy group, a sulfate group, a phosphate group or an alkanoyl group.
1 : A solid-phase carrier comprising:
a functional group capable of fixing a ligand; and
a group comprising:
a first component selected from the group consisting of a sulfinyl group, a sulfide group, an oxy group and an imino group; and
a second component selected from the group consisting of a hydroxyl group, a thiol group, an amino group, a carboxy group, a sulfate group, a phosphate group and an alkanoyl group.
2 : The solid-phase carrier according to claim 1 , wherein the functional group capable of fixing a ligand is a cyclic ether group, a carboxy group, a succinimidoxy group, a formyl group, an isocyanate group or an amino group.
3 : The solid-phase carrier according to claim 2 , wherein the functional group capable of fixing a ligand is the cyclic ether group, and
the cyclic ether group is a group represented by Formula (1-1), (1-2) or (1-3):
wherein
R 1 represents a divalent hydrocarbon group having 1 to 6 carbon atoms, and
* represents a bond.
4 : The solid-phase carrier according to claim 1 , wherein the second component is the hydroxyl group.
5 : The solid-phase carrier according to claim 1 , wherein the group comprising the first component and the second component is a group represented by Formula (2-1), (2-2) or (2-3):
wherein
R 1 represents a divalent hydrocarbon group having 1 to 6 carbon atoms,
R 2 represents a monovalent organic group having 1 to 10 carbon atoms,
X represents a sulfinyl group a sulfide group an oxy group or an imino group, and
** represents a bond.
6 : The solid-phase carrier according to claim 5 , wherein R 2 is a monovalent organic group represented by Formula (3):
wherein R 3 represents a divalent or trivalent organic group having 1 to 10 carbon atoms, and
n represents 1 or 2.
7 : The solid-phase carrier according to claim 5 , wherein X is a sulfinyl group or a sulfide group.
8 : The solid-phase carrier according to claim 1 , wherein the solid-phase carrier is a porous polymer particle.
9 : A method for producing a solid-phase carrier, the method comprising;
bringing a solid-phase carrier having a functional group capable of fixing a ligand into contact with a compound represented by Formula (4):
R 2 —Y—H (4)
wherein
R 2 represents a monovalent organic group having 1 to 10 carbon atoms, and
Y represents a sulfide group, an oxy group or an imino group, and
wherein the solid-phase carrier comprises a functional group capable of fixing a ligand and a group represented by Formula (5-1), (5-2) or (5-3):
wherein
R 1 represents a divalent hydrocarbon group having 1 to 6 carbon atoms,
R 2 represents a monovalent organic group having 1 to 10 carbon atoms, and
** represents a bond.
10 : The production method according to claim 9 , wherein Y is a sulfide group.
11 : The production method according to claim 10 , further comprising,
bringing the solid-phase carrier having the functional group capable of fixing a ligand and the group represented by Formula (5-1), (5-2) or (5-3) into contact with an oxidant to obtain a solid-phase carrier having a functional group capable of fixing a ligand and a group represented by Formula (6-1), (6-2) or (6-3):
wherein
R 1 represents a divalent hydrocarbon group having 1 to 6 carbon atoms,
R 2 represents a monovalent organic group having 1 to 10 carbon atoms, and
** represents a bond.
12 : The production method according to claim 9 , wherein the functional group is represented by Formula (1-1), (1-2) or (1-3):
wherein
R 1 represents a divalent hydrocarbon group having 1 to 6 carbon atoms, and
* represents a bond.
13 : A method for producing a filler the method comprising,
fixing a ligand to the solid-phase carrier according to claim 1 .
14 : The production method according to claim 13 , wherein the ligand is a protein or a peptide.
15 : A filler obtained by the production method according to claim 13 .
16 : A carrier comprising
a solid-phase carrier comprising a polymer and
a ligand or a reactive group for binding a ligand,
wherein
the ligand or the reactive group for binding a ligand is bound to the solid-phase carrier, and
the polymer has a terminal structure having at least one group selected from the group consisting of a hydroxyl group, a thiol group, a carbonyl group, an amino group, a thio group, a disulfide group, a sulfinyl group, a sulfonyl group, a carboxy group, a sulfate group, and a phosphate group, in the terminal of a polymer chain through a thio group, a sulfinyl group or a sulfonyl group.
17 : The carrier according to claim 16 ,
wherein the terminal structure is represented by Formula (21):
wherein
R 51 represents an organic group having 1 to 20 carbon atoms,
Z represents a hydroxyl group, a thiol group, an amino group, a carboxy group, a sulfate group, a phosphate group or an alkanoyl group, and
k represents an integer of 1 or more.
18 : The carrier according to claim 17 , wherein Z is a hydroxyl group, a thiol group, a carboxy group, a sulfate group or an alkanoyl group.
19 : The carrier according to claim 17 , wherein k is an integer of 1 to 5.
20 : The carrier according to any-ene claim 16 , wherein the terminal structure is introduced by adding a thiol compound before or during polymerization of the solid-phase carrier.
21 : The carrier according to claim 16 , wherein the polymer constituting the solid-phase carrier is a polymer having a structural unit derived from at least one monomer selected from the group consisting of a styrene-based monomer, a vinyl ketone-based monomer, a (meth)acrylonitrile-based monomer, a (meth)acrylate-based monomer, and a (meth)acrylamide-based monomer.
22 : The carrier according to claim 16 , wherein the solid-phase carrier further comprises a cross-linked structure derived from a cross-linking agent represented by Formula (22):
X 11 —R 52 —X 12 (22)
wherein
R 52 represents a divalent organic group having 1 to 10 carbon atoms, and
X 11 and X 12 independently represent a hydroxyl group, an amino group or a thiol group.
23 : The carrier according to claim 22 , wherein X 11 and X 12 are a thiol group.
24 : The carrier according to claim 23 , obtained by oxidizing a thio group in the cross-linked structure.
25 : The carrier according to claim 16 , wherein the ligand or the reactive group for binding a ligand is a ligand.
26 : The carrier according to claim 25 , wherein the ligand is an immunoglobulin-binding protein.
27 : A filler for a chromatography comprising the carrier according to claim 16 .
28 : A chromatography column, formed by filling a column container with the filler according to claim 15 .
29 : A method for refining a target substance, the method comprising:
preparing a composition comprising a target substance; and
passing the composition through the chromatography column according to claim 28 .
30 : The refining method according to claim 29 , wherein the target substance is a protein.
31 : A method for producing a filler, the method comprising,
fixing a ligand to a solid-phase carrier produced by the production method according to claim 9 .
32 : A filler obtained by the production method according to claim 31 .