Methods and compounds for detection and binding of aldehydes
Inventors
Shuhendler, Adam • SUCHY, Mojmir • DANG, Trina
Assignees
Publication Number
US-11696960-B2
Publication Date
2023-07-11
Expiration Date
2038-02-05
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Methods of detecting an aldehyde-containing compound in a subject or in a sample from a subject are described herein, comprising administering an aldehyde-binding compound of Formula I to the subject, or combining such a compound with the sample; and detecting the product of the compound of Formula I and the aldehyde-containing compound. Detection of the product may involve imaging, such as MRI, CEST-MRI or positron emission tomography (PET) imaging; or may involve fluorescence or an electrochemical detection method. Biologically relevant aldehydes detected according to the described method can be used to monitor conditions such as brain injury, neurodegenerative disorders such as Alzheimer's disease, diabetes, heart disease, and cancer.
Core Innovation
The invention provides methods and compounds for detecting an aldehyde-containing compound in a subject or in a sample from a subject by administering or combining an aldehyde-binding compound of Formula I with the subject or sample, and detecting the product formed from the reaction of the compound and the aldehyde-containing compound. Detection methods include imaging techniques such as MRI, CEST-MRI, and positron emission tomography (PET) imaging, as well as fluorescence and electrochemical detection methods.
The compounds of Formula I specifically bind to carbonyl-containing molecules, particularly aldehydes, under physiological conditions to form detectable products. These products can serve as markers of aldehyde presence related to various physiological or pathological conditions. The compounds include analogs of N-amino anthranilic acid and are characterized by the presence of functional groups that enable rapid reaction kinetics and stable product formation, facilitating detection.
The problem addressed is the limited availability of non-intrusive aldehyde detection technologies for diagnostic applications, especially methods capable of in vivo detection under physiological conditions. Existing methods such as blood and breath testing have limitations, and current imaging techniques, including CEST-MRI, face challenges detecting biologically significant functional groups like aldehydes. The invention aims to provide compounds and methods able to detect or bind aldehyde groups, overcoming these limitations.
Claims Coverage
The patent presents an independent claim focusing on a method for detecting freely diffusing small molecule aldehydes in a subject using specific aldehyde-binding compounds and detection techniques.
Method for detecting freely diffusing small molecule aldehydes in a subject
Administering an aldehyde-binding compound of Formula I to the subject and detecting the product of the compound with the freely diffusing small molecule aldehyde using MRI, CEST-MRI, or PET imaging.
Specifications of substituents in aldehyde-binding compounds
The aldehyde-binding compound includes specific substituents where Z is H or CH3, and the compound may be selected from defined structures within Formula I.
Target aldehydes for detection
The method detects freely diffusing small molecule aldehydes including glycolic acid, acetone, H2N—CH—CH—CO—H, malondialdehyde, crotonaldehyde, pyruvate, glyoxal, glyceraldehyde, DL-glyceraldehyde, glycoaldehyde, acetaldehyde, o-sulfobenzaldehyde, a secosterol, or 3-aminopropanal.
Detection of aldehydes indicative of brain injury and cell death
The brain injury comprises concussion, traumatic brain injury, or anoxic brain injury; the cell death detected is from chemotherapeutic killing of tumor cells.
Properties of aldehyde to be detected
The method detects freely diffusing small molecule aldehydes that are endogenous, have a molecular weight of less than 100, and are unbound to protein.
The claims cover a method employing aldehyde-binding compounds of Formula I with defined substituents to detect various freely diffusing small molecule aldehydes related to physiological and pathological conditions, using imaging modalities including MRI, CEST-MRI, and PET imaging.
Stated Advantages
The compounds and methods provide non-invasive, rapid, and selective detection of biologically relevant aldehydes under physiological conditions.
They produce substantial imaging contrast, allowing mapping and quantitation of aldehydes in living subjects.
The compounds enable in vivo derivatization of aldehydes, avoiding false positives caused by ex vivo derivatization methods.
The methods permit early detection and monitoring of diseases and conditions linked to aldehyde production, such as brain injury, neurodegeneration, cancer treatment efficacy, and cardiovascular disease.
The compounds can be modified for different detection modalities, including fluorescence, electrochemical detection, and radiolabeling for PET imaging.
Documented Applications
Detection of aldehydes resulting from brain injury including concussion, traumatic brain injury, and anoxic brain injury.
Monitoring neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease by detecting reactive aldehydes indicative of neurodegeneration.
Monitoring efficacy of cancer chemotherapy by detecting aldehydes produced from chemotherapeutic tumor cell killing.
Visualizing atherosclerotic plaque and inflammation related to heart disease.
Detecting ethylene glycol consumption toxicity by detecting glycolic acid, and potentially treating or preventing toxicity by binding toxic aldehydes.
Treating macular degeneration by binding aldehyde-containing compounds associated with the condition.
Providing point-of-care diagnostics via fluorescence and electrochemical detection methods for aldehyde quantification in biological fluids.
Use in flow cytometry for detection and characterization of cells based on aldehyde presence.
Interested in licensing this patent?