Biopolymer-mediated assembly of nanoparticles using genetically encoded proteins

Patent metadata

Field	Value
Publication number	US-10073087-B2
Application number	US-201514597575-A
Country	US
Kind code	B2
Filing date	Jan 15, 2015
Priority date	Jan 15, 2014
Publication date	Sep 11, 2018
Grant date	Sep 11, 2018

Abstract

Various aspects and embodiments provided herein are directed to compositions that include at least one nanoparticle linked to a first polypeptide, and a biologically synthesizable polymer linked to at least one second polypeptide that binds covalently to the first polypeptide. Other aspects and embodiments provided herein are directed to methods of producing the foregoing compositions and components therein.

First claim

What is claimed is:

1. A composition comprising:
(a) a first plurality of conjugates, wherein each conjugate of the first plurality comprises a nanoparticle linked to a first polypeptide; and
(b) a second plurality of conjugates, wherein each conjugate of the second plurality comprises an amyloid fibril subunit linked to a second polypeptide that is heterologous to the amyloid fibril subunit,
wherein each conjugate of the first plurality irreversibly binds to a conjugate of the second plurality through an isopeptide bond between the first and second polypeptides; and
wherein the amyloid fibril subunits assemble to form an amyloid fibril.

2. The composition of claim 1 , wherein the at least one nanoparticle comprises at least one material selected from a metal, a noble metal, an oxide, a semiconductor material, or a combination of two or more of the foregoing.

3. The composition of claim 2 , wherein the composition comprises at least one semiconductor material selected from cadmium sulfide (CdS), cadmium selenide (CdSe), cadmium telluride (CdTe), zinc sulfide (ZnS), zinc selenide (ZnSe), indium phosphide (InP), lead sulfide (PbS), and lead selenide (PbSe).

4. The composition of claim 1 , wherein the at least one nanoparticle comprises a core material and at least one shell material.

5. The composition of claim 1 , wherein the nanoparticle is linked to the first polypeptide through a peptide linker.

6. The composition of claim 5 , wherein the peptide linker is a dipeptide linker.

7. The composition of claim 6 , wherein the dipeptide linker is a cysteine-cysteine (Cys 2 ) linker or a histidine-histidine (His 2 ) linker.

8. The composition of claim 5 , wherein the peptide linker links a terminus of the first polypeptide to an external surface of the nanoparticle.

9. The composition of claim 8 , wherein the peptide linker links the N-terminus of the first polypeptide to an external surface of the nanoparticle.

10. The composition of claim 1 , wherein the amyloid fibril subunit is a CsgA protein subunit.

11. The composition of claim 1 , wherein the amyloid fibril has a length of one micron to five microns.

12. The composition of claim 1 , wherein one of the first and second polypeptides comprises a peptide tag, and the other of the first and second polypeptides comprises a protein.

13. The composition of claim 12 , wherein the protein is SpyCatcher and the peptide tag is SpyTag.

14. The composition of claim 13 , wherein the SpyTag comprises the sequence identified by SEQ ID NO: 8.

15. The composition of claim 12 , wherein the protein is pilin-C and the peptide tag is isopeptag.

16. The composition of claim 15 , wherein the isopeptag comprises the sequence identified by SEQ ID NO: 7.

Assignees

• Massachusetts Inst Technology

Inventors

• Deng Zhengtao
• Lu Timothy Kuan-Ta

Classifications

• A61K49/0093 Primary

  Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle · CPC title

• G01N33/521 Primary

  Single-layer analytical elements · CPC title