Leucine beta roll domains and uses thereof

Patent metadata

Field	Value
Publication number	US-10059934-B2
Application number	US-201514814102-A
Country	US
Kind code	B2
Filing date	Jul 30, 2015
Priority date	Nov 11, 2011
Publication date	Aug 28, 2018
Grant date	Aug 28, 2018

Abstract

In one aspect, the invention relates to a peptide that forms a calcium-dependent hydrogel using a rationally engineered beta roll peptide. In the absence of calcium, the peptide is intrinsically disordered. Upon addition of calcium, the peptide forms a corkscrew-like structure. In one embodiment, one face of the beta roll is mutated to comprise leucine residues. In some embodiments, a leucine zipper forming helical domain to the engineered beta roll forms hydrogels by physical cross-linking in calcium rich environments.

First claim

What is claimed is:

1. A beta roll comprising a modified scaffold from the wild-type RTX domain of adenylate cyclase from Bordetella pertussis , wherein said modified scaffold includes mutation of non-leucine residues to leucine.

2. A protein hydrogel network comprising the beta roll of claim 1 .

3. The protein hydrogel network of claim 2 , wherein the beta roll is fused to a leucine zipper with a soluble linker region.

4. The beta roll of claim 1 , wherein the beta roll domain comprises at least one repeating unit having a 9 amino acid residue sequence.

5. The beta roll of claim 4 , wherein the leucine mutations are introduced at radially protruding amino acids.

6. The beta roll of claim 5 , wherein at least 8 leucine mutations are introduced at radially protruding amino acids.

Assignees

• Univ Columbia

Inventors

• Banta Scott
• Blenner Mark A
• Wheeldon Ian
• Dooley Kevin

Classifications

• A61L27/50

  Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials} · CPC title

• C12N9/88 Primary

  Lyases (4.) · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• A61L15/44

  Medicaments · CPC title

• A61L15/60

  Liquid-swellable gel-forming materials, e.g. super-absorbents · CPC title