IP Library Granted Patent US 10,267,788
Granted Patent B1
US 10,267,788 · App. 14/159,308 · Granted Apr 23, 2019

Linear peptides that mimic structural epitopes for antibody assays

Inventors: Joseph S. Schoeniger (Oakland, CA); Peter Anderson (Bothell, WA)
Assignee: National Technology & Engineering Solutions of Sandia, LLC
G01N33/531C07K14/005
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Quick Facts
Patent No.
US 10,267,788
App. No.
14/159,308
Granted
Apr 23, 2019
Kind
B1
Abstract

A method including identifying one or more structures in adjacent sequences of one or more proteins that can be mimicked by a peptide; and assembling a peptide that mimics the one or more secondary structures. A method including assembling epitopes of linked pairs of discontiguous peptide subsequences that mimic one or more structures in sequences of a protein; and assaying antibodies against the epitopes.

Claims (20)

1. A method comprising:

identifying a non-linear epitope comprising one or more secondary structures in spatially adjacent discontiguous first and second subsequences of one or more proteins that can be mimicked by a synthesized peptide, wherein the first and second subsequences that define the peptide mimic include two to less than 10 amino acid residues, wherein the secondary structures in the spatially adjacent first and second subsequences are separated by a distance of 10 angstroms or less;

assembling a peptide that mimics the one or more secondary structures, wherein the secondary structures are stabilized using at least one covalent modification, wherein the secondary structures are linked together as part of a single synthesized peptide molecule by attaching peptide linkers to the C- and N-termini of the first and second subsequences and cross-linking the first and second subsequences, wherein the assembled peptide has less than 20 amino acid residues, and wherein the assembled peptide presents one or more binding sites to an antibody that binds to the epitope from which the subsequences have been excerpted; and

assaying a sample solution using the peptide to identify a presence of the one or more proteins that the peptide mimics in the sample solution.

2. The method of claim 1 , wherein the adjacent sequences are part of the same protein.

3. The method of claim 1 , wherein the peptide comprises a pair of subsequences of less than 10 amino acids from each of the adjacent sequences.

4. The method of claim 3 , wherein assembling comprises connecting the subsequences with a linker of less than five amino acids.

5. The method of claim 1 , wherein the one or more secondary structures are selected from the group consisting of a helix and a β hairpin.

6. A method comprising:

assembling epitopes of linked pairs of discontiguous peptide subsequences that mimic one or more structures in sequences of a protein,

wherein the subsequences that define the peptide mimic include two to less than 10 amino acid residues,

wherein the synthesized peptide has less than 20 amino acid residues,

wherein the linked pairs of discontiguous peptide subsequences are linked together as part of a single molecule by attaching peptide linkers to a C-termini and an N-termini of ones of the subsequences,

wherein the linked pairs of discontiguous peptide subsequences are formed into a secondary structure maintained by a cross-linker,

wherein the secondary structures are stabilized using at least one covalent modification, and

wherein the synthesized peptide presents one or more binding sites to antibodies that bind to each of the epitopes from which the subsequences have been excerpted; and

assaying antibodies against the epitopes to identify a presence of the antibodies in a solution.

7. The method of claim 6 , wherein each of the linked pairs of subsequences are less than 10 amino acids.

8. The method of claim 6 , wherein the one or more structures are selected from the group consisting of a helix and a β hairpin.

9. The method of claim 6 , wherein assembling comprises linking pairs of discontiguous subsequences with a linker of less than five amino acids.

Assignments (3)
CHANGE OF NAME Recorded Dec 20, 2018
From: SANDIA CORPORATION
To: NATIONAL TECHNOLOGY & ENGINEERING SOLUTIONS OF SANDIA, LLC
Reel/Frame 047967/0284 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 23, 2017
From: SCHOENIGER, JOSEPH S.; ANDERSON, PETER
To: SANDIA CORPORATION
Reel/Frame 041358/0149 →
CONFIRMATORY LICENSE Recorded Mar 26, 2015
From: SANDIA CORPORATION
To: U.S. DEPARTMENT OF ENERGY
Reel/Frame 035296/0342 →
Continuity (1)
Provisional Application 61759494 · Feb 1, 2013