IP Library Granted Patent US 8,021,570
Granted Patent B2
US 8,021,570 · App. 11/762,574 · Granted Sep 20, 2011

β-peptide lyotropic liquid crystals and methods of manufacture and use thereof

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Quick Facts
Patent No.
US 8,021,570
App. No.
11/762,574
Granted
Sep 20, 2011
Kind
B2
Abstract

The present invention provides materials and methods that make liquid crystal phases accessible with relatively short β-peptides in aqueous solvents.

Claims (66)

1. A lyotropic liquid crystal comprising a β-peptide.

2. The lyotropic liquid crystal according to claim 1 further comprising an aqueous solvent wherein the β-peptide forms a helix in the aqueous solvent.

3. A lyotropic liquid crystal comprising a β-peptide and an aqueous solvent, wherein β-peptide forms a helix in the aqueous solvent, and wherein the β-peptide is globally amphiphilic.

4. A lyotropic liquid crystal comprising a β-peptide and an aqueous solvent, wherein the β-peptide forms a helix in the aqueous solvent, and wherein the β-peptide is globally non-amphiphilic.

5. A method of providing a β-peptide-based lyotropic liquid crystal, comprising the step of combining β-peptides capable of self-assembly under conditions to allow the self-assembly to occur whereby a β-peptide-based lyotropic liquid crystal is provided.

6. The method according to claim 5 wherein the β-peptide-based lyotropic liquid crystal comprises a β-peptide selected from the group consisting of:

a β-peptide forming a globally amphiphilic helix;

R-(ACHC-ACHC-β 3 -hLys) n wherein n is 2-4 and R is β 3 -hTyr or β 3 -h-para-Cl-Phe;

β 3 -hTyr-(ACHC-AVHC-β 3 hLys) 2 or β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 3 ;

R-(ACHC-ACHC-β 3 -hLys) 3 wherein R is β 3 -hTyr or β 3 -h- para-Cl-Phe and β 3 -hLys at position 10 is substituted by β 3 -hGlu;

a β-peptide forming a globally non-amphiphilic helix;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 ;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-X-ACHC-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 or β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-ACHC-β 3 -hPhe-X-NH 2 , whereinX is a hydrophilic amino acid;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 or β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-ACHC-β 3 -hPhe-X-NH 2 , wherein X is β 3 -hGlu or β 3 -hGln;

β 3 -hTyr-β 3 -hPhe-ACHC-β 3 -hLys-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-ACHCβ 3 -hPhe-β 3 -hLys-NH 2 ;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-β 3 -hLys-ACHC-NH 2 ;

CH 3 (CH 2 ) n CONH-β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 3 wherein n is 0-5; and

biotin-β 3 -hG 1 y-β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 3 .

7. A liquid crystal device for detecting an analyte in a sample, comprising: (a) a sample chamber; and (b) a β-peptide-based lyotropic liquid crystal positioned within the sample chamber, wherein the β-peptide- based lyotropic liquid crystal comprises a β-peptide selected from the group consisting of:

a β-peptide forming a globally amphiphilic helix;

R-(ACHC-ACHC-β 3 -hLys) n wherein n is 2-4 and R is β 3 -hTyr or β 3 -h-para-Cl-Phe;

β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 2 or β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 3 ;

R-(ACHC-ACHC-β 3 -hLys) 3 wherein R is β 3 -hTyr or β 3 -h- para-Cl-Phe and β 3 -hLys at position 10 is substituted by β 3 -hGlu;

a β-peptide forming a globally non-amphiphilic helix;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 ;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-X-ACHC-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 or β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β-hLys-ACHC-ACHC-β 3 -hPhe-X-NH 2 , wherein X is a hydrophilic amino acid;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-X-ACHC-ACHC-β 3 -hPhe-NH 2 or β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-ACHC-β 3 -hPhe-X—NH 2 , wherein X is β 3 -hGlu or β 3 -hGln;

β 3 -hTyr-β 3 -hPhe-ACHC-β 3 -hLys-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-ACHC-β 3 -hPhe-β 3 hLys-NH 2 ;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-β 3 -hLys-ACHC-NH 2 ;

CH 3 (CH 2 ) n CONH-β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 3 wherein n is 0-5; and

biotin-β 3 -hGly-β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 3 .

8. A method of providing a network of self-assembled nanofibers, comprising the step of combining β-peptides capable of self-assembly under conditions to allow the self-assembly to occur whereby a network of self-assembled nanofibers is provided.

9. The method of claim 8 wherein at least one of the (β-peptides capable of self-assembly is a β-peptide selected from the group consisting of:

a β-peptide forming a globally amphiphilic helix;

R-(ACHC-ACHC-β 3 -hLys) n wherein n is 2-4 and R is β 3 -hTyr or β 3 -h-para-Cl-Phe;

β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 2 or β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 3 ;

R-(ACHC-ACHC-β 3 -hLys) 3 wherein R is β 3 -hTyr or β 3 -h-para-Cl-Phe and β 3 -hLys at position 10 is substituted by β 3 -hGlu;

a β-peptide forming a globally non-amphiphilic helix;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 ;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-X-ACHC-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 or β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β-hLys-ACHC-ACHC-β 3 -hPhe-X—NH 2 , wherein X is a hydrophilic amino acid;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-X-ACHC-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 or β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-ACHC-β 3 -hPhe-X-NH 2 , wherein X is β 3 -hGlu or β 3 -hGln;

β 3 -hTyr-β 3 -hPhe-ACHC-β 3 -hLys-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 ;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 ;

CH 3 (CH 2 ) n CONH-β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 3 wherein n is 0-5; and

biotin-β 3 -hGly-β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 3 .

10. A lyotropic liquid crystal comprising a β-peptide, wherein the β-peptide is selected from the group consisting of:

R-(ACHC-ACHC-β 3 -hLys) n wherein n is 2-4 and R is β 3 -hTyr or β 3 -h-para-Cl-Phe;

β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 2 or β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 3 ;

R-(ACHC-ACHC-β 3 -hLys) 3 wherein R is β 3 -hTyr or β 3 -h-para-Cl-Phe and β 3 -hLys at position 10 is substituted by β 3 -hGlu;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 ;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-X-ACHC-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 or β 3 - hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-ACHC-β 3 -hPhe-X-NH 2 , wherein X is a hydrophilic amino acid;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-X-ACHC-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 or β 3 - hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe- 13 3 -hLys-ACHC-ACHC-β 3 -hPhe-X-NH 2 , wherein X is β 3 -hGlu or β 3 -hGln;

β 3 -hTyr-β 3 -hPhe-ACHC-β 3 -hLys-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC- ACHC-β 3 -hPhe-β 3 -hLys-NH 2 ;

β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys- ACHC-β 3 -hLys-ACHC-NH 2 ;

CH 3 (CH 2 ) n CONH-β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 3 wherein n is 0-5; and

biotin-β 3 -hGly-β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 3 .

11. The lyotropic liquid crystal according to claim 10 wherein the β-peptide has the structure: R-(ACHC-ACHC-β 3 -hLys) n wherein n is 2-4 and R is β 3 -hTyr or β 3 -h-para-Cl-Phe.

12. The lyotropic liquid crystal according to claim 11 wherein the β-peptide is β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 2 or β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 3 .

13. The lyotropic liquid crystal according to claim 10 wherein the β-peptide has the structure: R-(ACHC-ACHC-β 3 -hLys) 3 wherein R is β 3 -hTyr or β 3 -h-para-Cl-Phe and β 3 -hLys at position 10 is substituted by β 3 -hGlu.

14. The lyotropic liquid crystal according to claim 10 wherein the β-peptide is β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 .

15. The lyotropic liquid crystal according to claim 10 wherein the β-peptide is β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-X-ACHC-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 or β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC- β 3 -hPhe-β 3 -hLys-ACHC-ACHC-β 3 -hPhe-X-NH 2 , wherein X is a hydrophilic amino acid.

16. The lyotropic liquid crystal according to claim 15 wherein X is β 3 -hGlu or β 3 -hGln.

17. The lyotropic liquid crystal according to claim 10 wherein the β-peptide is β 3 -hTyr-β 3 -hPhe-ACHC-β 3 -hLys-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-ACHC-β 3 -hPhe-β 3 -hLys-NH 2 .

18. The lyotropic liquid crystal according to claim 10 wherein the β-peptide is β 3 -hTyr-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-β 3 -hPhe-ACHC-β 3 -hPhe-β 3 -hLys-ACHC-β 3 -hLys-ACHC-NH 2 .

19. The lyotropic liquid crystal according to claim 10 wherein the β-peptide is CH 3 (CH 2 ) n CONH-β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 3 wherein n is 0-5.

20. The lyotropic liquid crystal according to claim 10 wherein the β-peptide is biotin-β 3 -hGly-β 3 -hTyr-(ACHC-ACHC-β 3 -hLys) 3 .

Assignments (5)
RELEASE OF SECURITY INTEREST Recorded Sep 4, 2014
From: CREDIT SUISSE AG
To: ALCATEL LUCENT (SUCCESSOR IN INTEREST TO ALCATEL-LUCENT N.V.)
Reel/Frame 033687/0150 →
SECURITY AGREEMENT Recorded Jan 30, 2013
From: ALCATEL LUCENT N.V.
To: CREDIT SUISSE AG
Reel/Frame 029737/0641 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 2, 2009
From: GELLMAN, SAMUEL H; POMERANTZ, WILLIAM C; ABBOTT, NICHOLAS
To: WISCONSIN ALUMNI RESEARCH FOUNDATION
Reel/Frame 023454/0184 →
EXECUTIVE ORDER 9424, CONFIRMATORY LICENSE Recorded Jan 18, 2008
From: NATIONAL SCIENCE FOUNDATION
To: FOUNDATION, WISCONSIN ALUMNI RESEARCH
Reel/Frame 020388/0230 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 18, 2007
From: KAMINSKI, STEPHEN
To: ALCATEL LUCENT
Reel/Frame 019443/0462 →