Protein aggregation inhibitor
The present invention provides a protein aggregation inhibitor for use in preventing aggregation of a protein, which contains a terminal sulfanyl group-containing sulfobetaine polymer having a repeat unit derived from a sulfobetaine monomer represented by the formula (II), and a noble metal particle, and in which the terminal sulfanyl group-containing sulfobetaine polymer is chemisorbed on the noble metal particle by the sulfanyl group (the groups in the following formula are as defined in the DESCRIPTION).
1. A protein aggregation inhibitor for use in preventing aggregation of a protein, the inhibitor comprising
a terminal sulfanyl group-containing sulfobetaine polymer having a repeat unit derived from a sulfobetaine monomer represented by the formula (II):
(in the formula (II), R 1 is a hydrogen atom or a methyl group, R 2 an alkyl group having 1-4 carbon atoms, R 3 and R 4 are each independently an alkyl group having 1-4 carbon atoms, R 5 is an alkyl group having 1-4 carbon atoms, and X is an —NH— group or an —O— group), and
a noble metal particle, wherein the terminal sulfanyl group-containing sulfobetaine polymer is chemisorbed on the noble metal particle by the sulfanyl group,
wherein the terminal sulfanyl group-containing sulfobetaine polymer is present in an amount of 5-60 parts by mass per 100 parts by mass of the noble metal particle.
2. The protein aggregation inhibitor according to claim 1 , wherein the terminal sulfanyl group-containing sulfobetaine polymer further has a carboxyl group.
3. The protein aggregation inhibitor according to claim 2 , wherein the noble metal is gold.
4. The protein aggregation inhibitor according to claim 2 , wherein the noble metal particle has an average particle size of 1-100 nm.
5. The protein aggregation inhibitor according to claim 1 , wherein the terminal sulfanyl group-containing sulfobetaine polymer is obtained by polymerizing monomer components comprising a sulfobetaine monomer represented by the formula (II) and a compound represented by the formula (III):
HOOC—R 6 —S—C(═S)—S—R 7 (III)
(in the formula (III), R 6 is an alkylene group having 1-8 carbon atoms and optionally having at least one substituent selected from the group consisting of a cyano group and a phenyl group, and R 7 is an alkyl group having 1-18 carbon atoms and optionally having at least one substituent selected from the group consisting of a carboxyl group and a phenyl group) to prepare a sulfobetaine polymer, and reducing the obtained sulfobetaine polymer.
6. The protein aggregation inhibitor according to claim 5 , wherein the noble metal is gold.
7. The protein aggregation inhibitor according to claim 5 , wherein the noble metal particle has an average particle size of 1-100 nm.
8. The protein aggregation inhibitor according to claim 1 , wherein the terminal sulfanyl group-containing sulfobetaine polymer has a weight average molecular weight of 3,000-140,000.
9. The protein aggregation inhibitor according to claim 8 , wherein the noble metal is gold.
10. The protein aggregation inhibitor according to claim 8 , wherein the noble metal particle has an average particle size of 1-100 nm.
11. The protein aggregation inhibitor according to claim 1 , wherein the noble metal is gold.
12. The protein aggregation inhibitor according to claim 11 , wherein the noble metal particle has an average particle size of 1-100 nm.
13. The protein aggregation inhibitor according to claim 1 , wherein the noble metal particle has an average particle size of 1-100 nm.
14. A protein aggregation inhibitor for use in preventing aggregation of a protein, comprising a noble metal particle having, on its surface, a group represented by the formula (I):
(in the formula (I), R 1 in the number of n are each independently a hydrogen atom or a methyl group, R 2 in the number of n are each independently an alkyl group having 1-4 carbon atoms, R 3 in the number of n are each independently an alkyl group having 1-4 carbon atoms, R 4 in the number of n are each independently an alkyl group having 1-4 carbon atoms, R 5 in the number of n are each independently an alkyl group having 1-4 carbon atoms, R 6 is an alkylene group having 1-8 carbon atoms and optionally having at least one substituent selected from the group consisting of a cyano group and a phenyl group, X in the number of n are each independently an —NH— group or an —O— group, and n is an average degree of polymerization of 10-500),
wherein the group represented by the formula (I) is present in an amount of 5-60 parts by mass per 100 parts by mass of the noble metal particle.
15. The protein aggregation inhibitor according to claim 14 , wherein, in the formula (I), R 1 is a hydrogen atom or a methyl group, R 2 an alkyl group having 1-4 carbon atoms, R 3 and R 4 are each independently an alkyl group having 1-4 carbon atoms, R 5 is an alkyl group having 1-4 carbon atoms, R 6 is alkylene having 1-8 carbon atoms, and X is an —NH— group or an —O— group.
16. The protein aggregation inhibitor according to claim 15 , wherein the noble metal is gold.
17. The protein aggregation inhibitor according to claim 15 , wherein the noble metal particle has an average particle size of 1-100 nm.
18. A method for producing a protein aggregation inhibitor for use in preventing aggregation of a protein, the method comprising polymerizing monomer components comprising a sulfobetaine monomer represented by the formula (II):
(in the formula (II), R 1 is a hydrogen atom or a methyl group, R 2 an alkyl group having 1-4 carbon atoms, R 3 and R 4 are each independently an alkyl group having 1-4 carbon atoms, R 5 is an alkyl group having 1-4 carbon atoms, and X is an —NH— group or an —O— group), and a compound represented by the formula (III):
HOOC—R 6 —S—C(═S)—S—R 7 (III)
(in the formula (III), R 6 is an alkylene group having 1-8 carbon atoms and optionally having at least one substituent selected from the group consisting of a cyano group and a phenyl group, and R 7 is an alkyl group having 1-18 carbon atoms and optionally having at least one substituent selected from the group consisting of a carboxyl group and a phenyl group) to prepare a sulfobetaine polymer,
reducing the obtained sulfobetaine polymer to prepare a terminal sulfanyl group-containing sulfobetaine polymer, and
mixing the obtained terminal sulfanyl group-containing sulfobetaine polymer and a noble metal particle.
19. The protein aggregation inhibitor according to claim 14 , wherein the noble metal is gold.
20. The protein aggregation inhibitor according to claim 14 , wherein the noble metal particle has an average particle size of 1-100 nm.