Protein-to-DNA Recoding for High-Throughput Peptide Sequencing

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current tools and technologies lack the ability to perform sensitive, accurate, and high-throughput proteomic analysis for protein and peptide characterization, which is crucial for early disease detection and treatment.

Innovation Solution

A method involving chemically-reactive conjugates that recode amino acid sequences into DNA polymers, utilizing cycle and recode nucleic acids to determine identity and positional information of peptides by coupling them to a solid support, cleaving and separating amino acids, and forming affinity complexes for sequencing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current tools and technologies are used for proteomic analysis, then existing methods can be applied, but sensitivity, accuracy, and throughput are insufficient for early disease detection

Engineering Contradiction:

Improveproteomic analysis accuracyVSAvoidanalysis throughput

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The proteomic analysis process is segmented into distinct stages: peptide coupling to solid support, iterative amino acid cleavage and identification, DNA polymer synthesis through recoding, and sequencing. Each stage is optimized independently, allowing parallel processing of multiple peptides simultaneously while maintaining high measurement precision through controlled sequential reactions

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

A chemically-reactive conjugate serves as an intermediary between amino acid residues and DNA polymers. This conjugate enables the recoding of amino acid sequences into complementary DNA sequences through controlled chemical reactions, bridging the gap between proteomic and genomic analysis methodologies to achieve both high accuracy and throughput

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If sensitive and accurate protein characterization is achieved, then early disease detection is enabled, but current technologies lack the necessary sensitivity and accuracy

Engineering Contradiction:

Improvedisease detection reliabilityVSAvoidanalysis method complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

Peptides are pre-coupled to solid supports with specific orientations before analysis begins. This preliminary immobilization step ensures that N-terminal amino acids are accessible for sequential cleavage and identification, establishing a reliable foundation for subsequent high-precision proteomic analysis and enabling consistent early disease detection

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent replaces traditional mechanical and manual proteomic analysis methods with chemically-driven automated processes. Chemically-reactive conjugates and controlled chemical reactions substitute for complex mechanical manipulation, reducing operational complexity while enhancing reliability through reproducible chemical transformations

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Productivity

If high-throughput proteomic analysis is implemented, then productivity is improved, but measurement precision and sensitivity may be compromised

Engineering Contradiction:

Improveproteomic analysis throughputVSAvoidprotein characterization accuracy

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The system performs self-verification through the recoding process. Each amino acid identification step generates corresponding DNA sequence information that can be verified through sequencing, creating an intrinsic quality control mechanism that maintains measurement precision even as throughput increases through parallel processing

Inventive Principle:

Principle #25Self-service

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 highly-parallel and high-throughput analysis of protein sequences, facilitating early disease detection and improving healthcare by providing sensitive and accurate characterization of proteomes.

Implementation Method 1

contacting the peptide with the chemically-reactive conjugate, thereby coupling the chemically-reactive conjugate to the N-terminal amino acid of the peptide to form a conjugate complex

Methodology Applied

Scientific EffectChemical bonding: Chemical Bonding

Implementation Method 2

contacting the immobilized amino acid complex with a binding agent, the binding agent comprising: a binding moiety for preferentially binding to the immobilized amino acid complex

Methodology Applied

Scientific EffectAffinity binding:

Implementation Method 3

forming an affinity complex, the affinity complex comprising an immobilized amino acid complex and the binding agent and thereby bringing the cycle tag into proximity with the recode tag within the affinity complex

Methodology Applied

Scientific EffectProximity effect:

Data Source

PatentUS20260002940A1Determination of protein information by recoding amino acid polymers into DNA polymers

Publication Date: 2026.01.01 ABRUS BIO INC

AI summary

The present disclosure relates to compositions of matter, methods, and systems for analyzing polymeric macromolecules, including polymeric macromolecules such as peptides, polypeptides, and proteins.