Computational design of self-assembling cyclic protein homo-oligomers

Patent metadata

Field	Value
Publication number	US-12194075-B2
Application number	US-202017028377-A
Country	US
Kind code	B2
Filing date	Sep 22, 2020
Priority date	Nov 16, 2016
Publication date	Jan 14, 2025
Grant date	Jan 14, 2025

Abstract

Described herein are polypeptides capable of self-assembling to form homo-oligomers, and methods for designing such polypeptides.

First claim

We claim:

1. A nucleic acid encoding a polypeptide comprising the amino acid sequence that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 40,
wherein the polypeptide is capable of self-assembly into homo-oligomers; and
wherein residues in bold font for SEQ ID NO: 40 are conserved in the polypeptide:
EEAELAYLLGELAYKLGEYRIAIRAYRIALKRDPNNAEAWYNLGNAYYKOGRYREAIEYYQKA LELDPNNAEAWYNLGNAYYERGEYEEAIEYYRKALRLDPNNADAMONLLNAKMREE (SEQ ID NO: 40).

2. The nucleic acid of claim 1 , wherein the polypeptide comprises the amino acid sequence having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 40.

3. The nucleic acid of claim 1 , wherein the polypeptide comprises the amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 40.

4. The nucleic acid of claim 1 , wherein the polypeptide comprises the amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 40.

5. The nucleic acid of claim 1 , wherein the polypeptide comprises the amino acid sequence having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 40.

6. A nucleic acid encoding a polypeptide capable of self-assembly into homo-oligomers, wherein the polypeptide comprises the amino acid sequence selected from the group consisting of SEQ ID NOS: 16-21, 34-35, 37, and 40.

7. The nucleic acid of claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 40.

8. An expression vector, comprising the nucleic acid of claim 1 operatively linked to a promoter.

9. A host cell comprising the expression vector of claim 8 .

10. A kit, comprising:
(a) the nucleic acid of claim 1 ; and
(b) a second nucleic acid that encodes a polypeptide comprising the amino acid sequence that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO:39.

11. A kit, comprising:
(a) the expression vector of claim 9 ; and
(b) a second expression vector comprising a second nucleic acid that encodes a polypeptide comprising the amino acid sequence that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO:39, wherein the second nucleic acid is operatively linked to a promoter.

12. An expression vector, comprising the nucleic acid of claim 6 operatively linked to a promoter.

13. A host cell comprising the expression vector of claim 12 .

14. A kit, comprising:
(a) the nucleic acid of claim 6 ; and
(b) a second nucleic acid that encodes a polypeptide comprising the amino acid sequence that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO:39.

15. A kit, comprising:
(a) the expression vector of claim 12 ; and
(b) a second expression vector comprising a second nucleic acid that encodes a polypeptide comprising the amino acid sequence that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO:39, wherein the second nucleic acid is operatively linked to a promoter.

16. An expression vector, comprising the nucleic acid of claim 7 operatively linked to a promoter.

17. A host cell comprising the expression vector of claim 16 .

18. A kit, comprising:
(a) the nucleic acid of claim 7 ; and
(b) a second nucleic acid that encodes a polypeptide comprising the amino acid sequence that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO:39.

19. A kit, comprising:
(a) the expression vector of claim 16 ; and
(b) a second expression vector comprising a second nucleic acid that encodes a polypeptide comprising the amino acid sequence that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO:39, wherein the second nucleic acid is operatively linked to a promoter.

Assignees

• Univ Washington

Inventors

• Baker David
• Fallas Jorge
• Ueda george
• Sheffler William H
• Nguyen Vanessa

Classifications

• G16B15/30

  Drug targeting using structural data; Docking or binding prediction · CPC title

• C07K14/00

  Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof · CPC title

• G16B5/00

  ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks · CPC title

• A61K38/03 Primary

  Peptides having up to 20 amino acids in an undefined or only partially defined sequence; Derivatives thereof · CPC title