Native Small-Molecule Screening for Binding Polypeptides
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Solution Overview
Problem
Current methods for developing antibodies against small analytes require laborious and expensive chemical conjugation of small molecules to carrier proteins, leading to structural changes and low success rates, limiting the availability of antibody-based diagnostics for these molecules.
Innovation Solution
A method for screening polypeptides that allows direct binding to target molecules without conjugation, using capture complexes to form complexes with polypeptides and target molecules, followed by separation and analysis, enabling high-throughput screening of polypeptide libraries for specific binding properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemical conjugation of small molecules to carrier proteins is performed, then polypeptides can be obtained for antibody development, but the process becomes laborious, expensive, and time-consuming with structural changes and low success rates
Solution Approach 1:
The invention extracts the small molecule analyte from the conjugation process entirely. Instead of conjugating small molecules to carrier proteins, the method uses small molecule analytes directly in their native form to screen phage display libraries, eliminating the conjugation step and its associated problems with structural changes and low success rates
Solution Approach 2:
The invention introduces an intermediary detection system using mass spectrometry to detect binding events. Instead of relying on traditional ELISA detection methods that require conjugated antigens, the method uses mass spectrometry to detect complexes formed between antibodies and native small molecule analytes, enabling direct screening without conjugation
2Reliability
If chemical conjugation of small molecules to carrier proteins is performed, then polypeptides can be obtained for antibody development, but the process becomes laborious and expensive
Solution Approach 1:
The invention removes the complex chemical conjugation process entirely from the antibody development workflow. By using native small molecule analytes directly in phage display screening, the method eliminates all steps related to linker synthesis, conjugation chemistry, and validation, dramatically simplifying the manufacturing process
Solution Approach 2:
The small molecule analyte serves itself as the screening target without requiring modification or conjugation to carrier proteins. The analyte's native structure is sufficient for binding assays when detected via mass spectrometry, eliminating the need for external conjugation services and complex chemical processing
3Reliability
If chemical conjugation of small molecules to carrier proteins is performed, then polypeptides can be obtained for antibody development, but structural changes occur and success rates decrease
Solution Approach 1:
The invention extracts the small molecule analyte from the conjugation process and uses it in its native, unmodified form. By eliminating the conjugation step, the method prevents all structural changes that would otherwise occur to the analyte, including modifications from linkers and potential denaturation of the target structure
Solution Approach 2:
The invention creates a functional copy of the conjugation system's purpose through mass spectrometry detection. Instead of physically conjugating the analyte to a carrier protein for detection, the method detects the binding interaction through mass spectral analysis of the complex, preserving the analyte's native structure while achieving the same detection goal
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
Facilitates the development of polypeptides, such as antibodies, that can bind small molecules efficiently, eliminating the need for chemical conjugation, reducing costs and increasing throughput, and allowing analysis of multiple molecules simultaneously.
Implementation Method 1
allowing a capture complex to contact with a polypeptide thereby forming a first complex comprising the capture complex and the polypeptide
Implementation Method 2
allowing the first complex to contact with a sample comprising target molecules thereby forming a second complex comprising the capture complex, the polypeptide, and a target molecule
Implementation Method 3
separating the target molecule of the second complex to a solution
Data Source
AI summary
The present invention relates to the fields of life sciences, polypeptide analysis and polypeptide discovery methods. Also, the present invention concerns detection methods of target molecules in a sample. Specifically, the invention relates to a method of screening polypeptides capable of binding a target molecule and a method of analyzing or pretreating a sample. Also, the present invention relates to a kit for carrying out methods of the present invention as well as to a polypeptide, antibody or antigen binding fragment capable of binding target molecules screened or obtained by the method of the present invention.