1. An immobilization compound of formula (I)
or a salt thereof, wherein
X is N or C(R9);
R1, R2, R3 are independently selected from the group consisting of H or C1-4 alkyl;
R4, R5, R6, R7, R8, R9 are independently selected from the group consisting of H; halogen; C1-4 alkyl; OC1-4 alkyl; OH, wherein C1-4 alkyl is optionally substituted with one or more R10;
R10 is halogen, OH or C1-4 alkyl; and
A is
wherein each R11 is independently selected from the group consisting of H; halogen;
C1-4 alkyl; OC1-4 alkyl; OH, wherein C1-4 alkyl is optionally substituted with one or more R10;
n is 0, 1 or 2; and m is 1 or 2.
2. The immobilization compound of claim 1, selected from the group consisting of
3. A method for the preparation of an immobilization product, comprising immobilizing at least one immobilization compound according to claim 1 on a solid support.
4. The method of claim 3, wherein the solid support is selected from the group consisting of agarose, modified agarose, sepharose beads, latex, cellulose, and ferro- or ferrimagnetic particles.
5. The method of claim 3, wherein the immobilization product results from a covalent direct or linker mediated attachment of the immobilization compound to the solid support,.
6. The method of claim 3, wherein said immobilization occurs via the ring nitrogen atom of the residue A in formula (I).
7. An immobilization product, comprising the immobilization compound of claim 1 immobilized on a solid support.
8. A method for the identification of a JAK interacting compound, comprising the steps of
a) providing a protein preparation containing JAK,
b) contacting the protein preparation with the immobilization product of claim 7 under conditions allowing the formation of a complex between JAK and the immobilization product,
c) incubating the complex with a given compound, and
d) determining whether the compound is able to separate JAK from the immobilization product.
9. A method for the identification of a JAK interacting compound, comprising the steps of
a) providing a protein preparation containing JAK,
b) contacting the protein preparation with the immobilization product of claim 7 and with a given compound under conditions allowing the formation of a complex between JAK and the immobilization product, and
c) detecting the complex formed in step b).
10. A method for the identification of a JAK interacting compound, comprising the steps of:
a) providing two aliquots of a protein preparation containing JAK,
b) contacting one aliquot with the immobilization product of claim 7 under conditions allowing the formation of a complex between JAK and the immobilization product,
c) contacting the other aliquot with the immobilization product and with a given compound under conditions allowing the formation of the complex, and
d) determining the amount of the complex formed in steps b) and c).
11. The method of claim 10, wherein a reduced amount of the complex formed in the aliquot incubated with the compound in comparison to the aliquot not incubated with the compound indicates that JAK interacts with the compound.
12. The method of claim 10, wherein the amount of the complex is determined by separating JAK from the immobilization product and subsequent detection of separated JAK or subsequent determination of the amount of separated JAK.
13. The method of claim 12, wherein JAK is detected or the amount of JAK is determined by mass spectrometry or immunodetection methods.
14. The method of claim 10, performed as a medium or high throughput screening.
15. The method of claim 10, wherein said given compound is selected from the group consisting of synthetic compounds, or organic synthetic drugs, and natural small molecule compounds.
16. The method of claim 10, wherein the given compound is a JAK inhibitor.
17. The method of claim 10, wherein the JAK is JAK2 or JAK3.
18. A method for the identification of a JAK interacting compound, comprising the steps of:
a) providing two aliquots comprising each at least one cell containing JAK,
b) incubating one aliquot with a given compound,
c) harvesting the cells of each aliquot,
d) lysing the cells in order to obtain protein preparations,
e) contacting the protein preparations with the immobilization product of claim 7 under conditions allowing the formation of a complex between JAK and the immobilization product, and
f) determining the amount of the complex formed in each aliquot in step e).
19. A method for the purification of JAK, comprising the steps of
a) providing a protein preparation containing JAK,
b) contacting the protein preparation with the immobilization product of claim 7 under conditions allowing the formation of a complex between JAK and the immobilization product, and
c) separating JAK from the immobilization product.
20. A method for determining the presence of JAK in a sample, comprising the steps of:
a) providing a protein preparation expected to contain JAK,
b) contacting the protein preparation with the immobilization product of claim 8 under conditions allowing the formation of a complex between JAK and the immobilization product, and
c) detecting whether JAK has formed a complex with the immobilization product.
21. A kit comprising the immobilization compound according to any of claim 1 or 2 or the immobilization product according to claim 7 and one or more further auxiliary components.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed is:
1. A vehicular power window regulator, the regulator comprising:
a guide rail fixed to a lower end of a door glass;
a main arm and a sub arm connected for linear motion on the guide rail and mounted crosswise;
a driving motor connected to a sector gear mounted underneath the main arm to rotate the main arm; and
flex means for providing flexibility to a connection area between the main arm and the guide rail when the door glass vertically moves.
2. The regulator as defined in claim 1, wherein the flex means comprises:
a slider mounted on the guide rail for linear movement;
a slide shaft rotatably mounted on the slider; and
a grip, having an inner circumferential surface thereof and placed over the slide shaft opposite the slider and an external circumferential surface thereof inserted into the main arm, for connecting an area between the slide shaft and the main arm.
3. The regulator as defined in claim 2, wherein the slide shaft is formed at one side thereof with a spherical ball part while the slider is formed with a spherical ball groove for the ball part to be rotatably inserted thereinto.
4. The regulator as defined in claim 2, wherein the grip is centrally hollowed for the rod part to be inserted thereinto and is plurally split at one side thereof for sustaining a resilience of predetermined strength, and is provided at a circumferential peripheral surface thereof with a recess for being inserted into the hitching groove of the main arm.
5. The regulator as defined in claim 4, wherein the grip is tapered at a predetermined angle from the split side to the other side for easy insertion into the hitching groove, while the slider shaft is formed at a tip end thereof with a hitching jaw to prevent the grip from being detached therefrom.