Double-Labeled Peptide Standards for PTM Quantitation

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Solution Overview

Problem

Existing methods for detecting and quantifying post-translational modifications (PTMs) such as glycosylation in peptides are inefficient and require multiple devices and steps, leading to product loss and reduced specificity.

Innovation Solution

A method and device for enriching glycan-modified macromolecules using a single device with integrated hydrophilic interaction liquid chromatography (HILIC) and reverse phase chromatography, allowing for simpler and more specific isolation of glycopeptides with reduced material transfer and loss.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If multiple devices and steps are used for detecting and quantifying PTMs, then measurement precision can be improved, but device complexity increases and product loss increases

Engineering Contradiction:

ImprovePTM detection precisionVSAvoidnumber of devices and steps

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent combines HILIC and reverse phase chromatography into a single integrated device, eliminating the need for multiple separate chromatography systems. This merging reduces device complexity while maintaining the ability to enrich and detect glycan-modified macromolecules with high precision through coordinated use of both chromatographic modes.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The integrated device performs multiple functions including enrichment of glycan-modified macromolecules, separation of glycopeptides, and preparation for mass spectrometry analysis within a single platform. This multi-functionality reduces the number of steps and devices required while maintaining measurement precision for PTM detection.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Measurement precision

If multiple devices and steps are used for enriching glycan-modified macromolecules, then measurement precision can be improved, but loss of substance increases

Engineering Contradiction:

Improveglycopeptide identification precisionVSAvoidproduct loss

Core Design Contradiction:

Measurement precisionVSLoss of substance

Solution Approach 1:

By integrating HILIC and reverse phase chromatography into a single device, the patent eliminates multiple transfer steps between different chromatography systems. This reduces opportunities for material loss during transfer while maintaining the enrichment capability and identification precision of glycopeptides through the coordinated chromatographic separation.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The integrated device enables continuous processing of biological samples through glycan-modified macromolecule enrichment and glycopeptide separation without interrupting the workflow for device transfers. This continuous operation minimizes material loss while maintaining high precision in glycopeptide identification and quantification.

Inventive Principle:

Principle #20Continuity of useful action

3Measurement precision

If multiple steps are used for enriching glycan-modified macromolecules, then measurement precision can be improved, but loss of time increases

Engineering Contradiction:

ImprovePTM quantification precisionVSAvoidenrichment process time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The integration of HILIC and reverse phase chromatography into a single device consolidates multiple enrichment steps into one continuous process. This eliminates the time required for transferring samples between different chromatography systems while maintaining the precision of PTM quantification through the combined separation capabilities.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The integrated device enables continuous enrichment and separation of glycan-modified macromolecules without interruptions for device changes or transfers. This continuous operation reduces the overall time required for the enrichment process while maintaining measurement precision through consistent and coordinated chromatographic separation.

Inventive Principle:

Principle #20Continuity of useful action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables efficient and specific enrichment of glycopeptides with higher specificity and peptide structure match, reducing the number of steps and material loss, suitable for large-scale production and integration into automated platforms.

Implementation Method 1

subjecting the biological sample to hydrophilic interaction liquid chromatography (HILIC)

Methodology Applied

Scientific EffectHydrophilic interaction liquid chromatography: Chromatography

Implementation Method 2

reverse phase chromatography

Methodology Applied

Scientific EffectReverse phase chromatography: Chromatography

Data Source

PatentUS20250271448A1Methods for identifying or quantitating peptides

Publication Date: 2025.08.28 PROGNOMIQ INC

AI summary

Provided are methods comprising combining a biological sample with a double-labeled peptide standard comprising a peptide comprising a first label and comprising a post-translational modification (PTM) comprising a second label; and identifying or measuring, based on the double-labeled peptide standard, an endogenous protein of the biological sample, wherein the endogenous protein comprises the PTM. Further, provided are methods and devices for enriching and/or purifying glycan-modified macromolecules with higher specificity and sensitivity.