Resorcinarene-based amphipathic compound and use thereof

Patent metadata

Field	Value
Publication number	US-10793589-B2
Application number	US-201716344852-A
Country	US
Kind code	B2
Filing date	Mar 17, 2017
Priority date	Oct 28, 2016
Publication date	Oct 6, 2020
Grant date	Oct 6, 2020

Abstract

The present invention relates to a newly developed resorcinarene-based amphipathic compound, a method for producing the same, and a method for extracting, solubilizing, stabilizing, crystallizing, or analyzing a membrane protein by using the same. In addition, compared to a conventional compound, the compound can efficiently extract, from a cell membrane, membrane proteins having a greater variety of structures and characteristics, and can stably store such membrane proteins for a long time in an aqueous solution. Therefore, the compound can be used to analyze the functions and structures of such membrane proteins. Analysis of the structures and functions of membrane proteins, being closely related to the development of new drugs, is one of the fields of greatest interest in biology and chemistry today.

First claim

What is claimed is:

1. A compound represented by the following Formula 1 or Formula 2:

wherein R 1 to R 4 are each independently a substituted or unsubstituted C 3 -C 30 alkyl group, a substituted or unsubstituted C 3 -C 30 cycloalkyl group, or a substituted or unsubstituted C 3 -C 30 aryl group;
X 1 to X 8 are saccharides; and
m 1 to m 8 are 0, 1, or 2,

wherein R 1 to R 4 are each independently a substituted or unsubstituted C2-C30 alkyl group, a substituted or unsubstituted C 3 -C 30 cycloalkyl group, or a substituted or unsubstituted C 3 -C 30 aryl group;
X 1 to X 4 are saccharides; and
m 1 to m 4 are 0, 1, or 2.

2. The compound of claim 1 , wherein the saccharide is a monosaccharide or a disaccharide.

3. The compound of claim 1 , wherein the saccharide is glucose or maltose.

4. The compound of claim 1 , wherein R 1 to R 4 are each independently said substituted or unsubstituted alkyl group; X 1 to X 8 are glucoses or maltoses; and m 1 to m 8 are 1.

5. The compound of claim 1 , which is a compound represented by one of the following Formulas 3 to 14:

6. The compound of claim 1 , wherein the compound is an amphipathic molecule for extracting, solubilizing, stabilizing, crystallizing, or analyzing a membrane protein.

7. The compound of claim 1 , wherein the compound has a critical micelle concentration (CMC) of 0.0001 to 1 mM in an aqueous solution.

8. A composition for extracting, solubilizing, stabilizing, crystallizing, or analyzing a membrane protein, comprising the compound according to claim 1 .

9. The composition of claim 8 , wherein the composition is prepared in a form of micelles, liposomes, emulsions or nanoparticles.

10. A method of preparing a compound represented by the following Formula 1, comprising:
1) introducing an alkyl group by acid-catalyzed condensation of four 1,3-bis(2-hydroxyethoxy)benzene compounds;
2) introducing a protective group-attached saccharide by glycosylating the product of step 1); and
3) de-protecting the product of step 2):

wherein R 1 to R 4 are each independently a substituted or unsubstituted C 3 -C 30 alkyl group, a substituted or unsubstituted C 3 -C 30 cycloalkyl group, or a substituted or unsubstituted C 3 -C 30 aryl group;
X 1 to X 8 are saccharides; and
m 1 to m 8 are 0, 1, or 2.

11. The method of claim 10 , wherein R 1 to R 4 are each independently a substituted or unsubstituted C 3 -C 30 alkyl group; X 1 to X 8 are glucoses;
and m 1 to m 8 are 1.

12. A method of preparing a compound represented by the following Formula 2, comprising:
1) introducing an alkyl group by acid-catalyzed condensation of four methyl resorcinol compounds;
2) subjecting the product of step 1) to a methylene bridging reaction using bromochloromethane;
3) brominating a benzylic position in the product of step 2);
4) hydrolyzing or causing the product of step 3) to have ethylene glycol linkages;
5) introducing a protective group-attached saccharide by glycosylating the product of step 4); and
6) de-protecting the product of step 5):

wherein R 1 to R 4 are each independently a substituted or unsubstituted C 2 -C 30 alkyl group, a substituted or unsubstituted C 3 -C 30 cycloalkyl group, or a substituted or unsubstituted C 3 -C 30 aryl group;
X 1 to X 4 are saccharides; and
m 1 to m 4 are 0, 1, or 2.

13. A method of extracting, solubilizing, stabilizing, crystallizing, or analyzing a membrane protein, the method comprising treating a membrane protein with a compound represented by the following Formula 1 or Formula 2 in an aqueous solution:

wherein R 1 to R 4 are each independently a substituted or unsubstituted C 3 -C 30 alkyl group, a substituted or unsubstituted C 3 -C 30 cycloalkyl group, or a substituted or unsubstituted C 3 -C 30 aryl group;
X 1 to X 8 are saccharides; and
m 1 to m 8 are 0, 1, or 2,

wherein R 1 to R 4 are each independently a substituted or unsubstituted C 2 -C 30 alkyl group, a substituted or unsubstituted C 3 -C 30 cycloalkyl group, or a substituted or unsubstituted C 3 -C 30 aryl group;
X 1 to X 4 are saccharides; and
m 1 to m 4 are 0, 1, or 2.

14. The method of claim 13 , wherein R 1 to R 4 are each independently said substituted or unsubstituted alkyl group; X 1 to X 8 are glucoses or maltoses; and m 1 to m 8 are 1.

15. The method of claim 13 , wherein the membrane protein is a uric acid-xanthine/Hxanthine/H + symporter (UapA), a leucine transporter (LeuT), a human β 2 adrenergic receptor (β 2 AR), a melibiose permease (MelB), or a combination of two or more thereof.

Assignees

• Iucf Hyu Erica Campus

Inventors

• Chae Pil Seok
• Hussain Hazrat

Classifications

• G01N33/6842

  Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins · CPC title

• C07H15/18 Primary

  Acyclic radicals, substituted by carbocyclic rings · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• C07K1/145

  by extraction or solubilisation · CPC title

• C07K14/705

  Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} · CPC title