IP Library Granted Patent US 7,670,784
Granted Patent B2
US 7,670,784 · App. 11/794,124 · Granted Mar 2, 2010

β-Benzyloxyaspartic acid derivatives having two substituents on their benzene rings

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Quick Facts
Patent No.
US 7,670,784
App. No.
11/794,124
Granted
Mar 2, 2010
Kind
B2
Abstract

The present invention provides a β-benzyloxyaspartic acid derivative having two substituents on its benzene ring, wherein the derivative has L-glutamate uptake inhibitory effect. More specifically, the present invention provides a compound of Formula (1) having an inhibitory effect against the glutamate uptake activity of L-glutamate transporters (wherein R 1 represents an optionally substituted aromatic group, and substituent R 2 represents a group selected from an optionally substituted linear or branched C 1 -C 30 aliphatic group whose chain may contain nitrogen or oxygen, and an optionally substituted aromatic group) or a salt thereof, and a method for obtaining the above compound, as well as a method for purifying or detecting L-glutamate transporters using the above compound.

Claims (27)

1. A compound of Formula (1) or a salt thereof:

wherein R 1 represents an optionally substituted aromatic group; and

substituent R 2 represents a group selected from an optionally substituted linear or branched C 1 -C 30 aliphatic group whose chain may contain nitrogen or oxygen, and an optionally substituted aromatic group.

2. The compound according to claim 1 , wherein the substituent R 2 is substituted with an amino group at its end.

3. The compound according to claim 1 , wherein the substituent R 2 is an aliphatic group having an oxygen atom and a nitrogen atom within its chain.

4. The compound according to claim 1 , wherein the compound of Formula (1) is (2S,3S)-3-(3-(6-(6-(2-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethoxy)acetamido)hexanamido) hexanamido)-5-(4-(trifluoromethyl)benzamido)benzyloxy)aspartic acid.

5. An affinity column ligand comprising the compound according to claim 1 .

6. An affinity column ligand comprising the compound according to claim 4 .

7. A ligand for fluorescence detection, comprising the compound according to claim 1 .

8. A ligand for fluorescence detection, comprising the compound according to claim 4 .

9. A method for purifying a L-glutamate transporter protein in a biological sample, which comprises the steps of:

preparing an affinity column by using the compound according to claim 2 as an affinity column ligand having a free amino group and allowing the compound to bind to a column carrier reactive with a free amino group;

contacting a biological sample likely to contain a L-glutamate transporter protein with the affinity column;

washing the affinity column; and

eluting the L-glutamate transporter protein from the affinity column.

10. The method according to claim 9 , wherein the compound of Formula (1) (2S,3S)-3-(3-(6-(6-(2-(2-(242-(2-aminoethoxy)ethoxy)ethoxy)ethoxy)acetamido)hexanamido) hexanamido)-5-(4-(trifluoromethyl)benzamido)benzyloxy)aspartic acid is used as an affinity column ligand.

11. A method for purifying a L-glutamate transporter protein in a biological sample, which comprises the steps of:

preparing a column by allowing the compound having a free amino group according to claim 2 to bind to biotin and then holding the resulting bound product on an avidin column;

contacting a biological sample likely to contain a L-glutamate transporter protein with the column;

washing the column; and

eluting the L-glutamate transporter protein from the column.

12. The method according to claim 11 , wherein the compound of Formula (1) (2S,3S)-3-(3-(646-(2-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethoxy)acetamido)hexanamido) hexanamido)-5-(4-(trifluoromethyl)benzamido)benzyloxy)aspartic acid is used as a column ligand.

13. A fluorescence-based method for detecting a L-glutamate transporter protein, which comprises the steps of:

allowing the compound according to claim 1 to bind to biotin, and then allowing the resulting bound product to bind to a fluorescent group or fluorescently-labeled avidin;

contacting a biological sample likely to contain a L-glutamate transporter protein with the bound product; and

fluorescently detecting the presence or absence of binding with the biotin-avidin bound product in the sample.

14. The method according to claim 13 , wherein the compound of Formula (1) (2S,3S)-3-(3-(6-(6-(2-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethoxy)acetamido)hexanamido) hexanamido)-5-(4-(trifluoromethyl)benzamido)benzyloxy)aspartic acid is used.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 30, 2009
From: SUNTORY LIMITED
To: SUNTORY HOLDINGS LIMITED
Reel/Frame 022653/0665 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 26, 2007
From: SHIMAMOTO, KEIKO
To: SUNTORY LIMITED
Reel/Frame 019521/0214 →