US 10,883,982 B2Granted

Methods for determining molecule folding associated with proteopathies

AssigneeArizona Board of Regents on Behalf of the University of Arizona

InventorsJacob Schwartz, John C. Jewett, Mahta Moinpour, Mehrdad Shadmehr

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Abstract

Methods, systems, and compositions for detecting molecule aggregation, folding, or interactions featuring comparing the amount of labeling of a molecule of interest, such as a protein, in a test sample with an amount of labeling in a control, e.g., a sample wherein the molecule of interest is denatured. If less labeling is present in the test sample as compared to the control sample, the test sample may comprise the molecule of interest in aggregate form, folded form, or interactive form, e.g., interacting with another molecule such as a protein molecule, DNA molecule or RNA molecule. The present invention may be used for detecting or monitoring a disease or condition such as a protein misfolding disease (proteopathy), e.g., amyotrophic lateral sclerosis (ALS), etc.

Claims12

Dependent claims

A method of detecting the presence of occluded amino acids in a protein associated with a proteopathy in a test sample, said method comprising:

a. subjecting the test sample to a reaction adapted to covalently modify tyrosines with a first reactive moiety conjugated to a first detectable label;
b. subjecting the test sample to denaturing conditions after labeling the sample with the first reactive moiety conjugated to the first detectable label;
c. subjecting the test sample to a reaction adapted to covalently modify tyrosines with the first reactive moiety conjugated to a second detectable label after subjecting the sample to denaturing conditions, wherein the first detectable label and second detectable label are visually distinct;
and
d. making visible the first detectable label and second detectable label;
wherein the presence of the second detectable label in addition to the first detectable label is indicative of the presence of occluded tyrosines in the protein associated with a proteopathy in the test sample.

3 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/158,074Filed 11 Oct 2018 · continuation in part
Priority: 13 Apr 2016
Published: US 2019/0041385 A17 Feb 2019
Granted: 5 Jan 2021
Term ends: Not estimatedThe source records don’t support an estimate.

Classification14 codes

G01N 33/533
Production of labelled immunochemicals: with fluorescent label
C07K 1/1136
Without change of the primary structure: by reversible modification of the secondary, tertiary or quarternary structure, e.g. using denaturating…
C07K 1/13
General methods for the preparation of peptides , i.e. processes for the organic chemical preparation of peptides or proteins of any length:…
G01N 33/52
Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing: use of…

Family

Application62/322,148Us provisional application · filed 13 Apr 2016
Application62/373,278Us provisional application · filed 10 Aug 2016
Application62/383,310Us provisional application · filed 2 Sep 2016
PCT/US2017/027444Parent of this continuation-in-part · filed 13 Apr 2017
PCT/US2017/027485Parent of this continuation-in-part · filed 13 Apr 2017
PCT/US2017/027472Parent of this continuation-in-part · filed 13 Apr 2017
US 2019/0041385 A1Pre-grant publication · published 7 Feb 2019
US 10,883,982 B2This patent

From the US filing history. Foreign family members aren’t listed.