Antibodies for Intrinsically Disordered Pro/Ala Sequences
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods fail to generate specific binding moieties, such as antibodies, against intrinsically disordered proteins and protein domains, particularly Pro/Ala-rich sequences, which are immunologically inert and challenging to immunize against due to their lack of immunogenicity.
Innovation Solution
A method involving immunization of non-human mammals with antigens conjugated to immunoadjuvants, using Pro/Ala peptides with a protecting group attached, to elicit a specific antibody response against intrinsically disordered peptides and proteins, overcoming the immunological inertness of these sequences.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunization methods are used against intrinsically disordered proteins, then the immunization process is simple, but no specific antibody response is generated due to immunological inertness
Solution Approach 1:
The patent employs structured carrier proteins as intermediaries to bridge the gap between intrinsically disordered antigens and the immune system. The carrier proteins provide stable epitopes that can be recognized by antibodies, while the disordered regions are presented in a context that enables immune recognition. This mediator approach allows antibody generation against targets that would otherwise be immunologically inert.
Solution Approach 2:
The invention changes the physical and chemical parameters of the antigen presentation by using specific carrier proteins with defined structural properties. By controlling parameters such as carrier protein structure, antigen-to-carrier ratio, and conjugation chemistry, the method transforms non-immunogenic disordered regions into immunogenic complexes that elicit specific antibody responses.
2Reliability
If intrinsically disordered sequences are used as antigens, then the antigen structure is flexible and adaptable, but the antigen lacks immunogenicity
Solution Approach 1:
The patent merges intrinsically disordered antigen sequences with stable structured carrier proteins to create hybrid antigen complexes. This combination allows the disordered regions to maintain their flexibility and adaptability while the carrier provides the structural stability needed for immune recognition. The merged complex exhibits both properties simultaneously, enabling immunogenicity without losing the functional characteristics of the disordered regions.
3Reliability
If antibodies are generated against structured proteins, then high antibody specificity is achieved, but antibodies cannot bind to disordered protein sequences
Solution Approach 1:
The invention introduces dynamics into antibody generation by using disordered antigen regions that can adopt multiple conformations. The resulting antibodies are capable of binding to flexible, dynamic targets rather than rigid structured proteins. This dynamic approach expands the antibody target range to include intrinsically disordered proteins while maintaining binding capability through the carrier-mediated presentation of epitopes.
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
The approach successfully generates antibodies that specifically bind to Pro/Ala-rich sequences, enabling diagnostic and research applications by overcoming the immunological inertness of these proteins, demonstrating high affinity and specificity.
Implementation Method 1
The present invention relates to a method for generating and/or obtaining specific binding moieties against intrinsically disordered proteins (IDPs) and/or intrinsically disordered protein domains which tend to be immunologically inert and lack immunogenicity in animals, in particular in mammals
Implementation Method 2
wherein a protecting group RN is attached to the N-terminal amino group of said peptide
Data Source
AI summary
The present invention relates to a method for generating and/or obtaining specific binding moieties against intrinsically disordered proteins (IDPs) and/or intrinsically disordered protein domains which tend to be immunologically inert and lack immunogenicity in animals, in particular in mammals. The present invention also relates to such specific binding moieties, in particular to antibodies and/or to antigen binding fragments thereof, specifically binding to structurally disordered and/or intrinsically disordered sequences, in particular to Pro/Ala-rich sequences (PAS). These binding moieties, antibodies, antigen binding fragments are first in class since they bind to/recognize disordered peptides or polypeptide fragments as also comprised in such “intrinsically disordered proteins”, in particular PAS polypeptides. The inventive binding moieties, antibodies, antigen binding fragments are, without being limiting, particularly useful in diagnostic settings as well as research tools. The present invention relates to a method for generating and/or obtaining specific binding moieties against intrinsically disordered proteins (IDPs) and/or intrinsically disordered protein domains which tend to be immunologically inert and lack immunogenicity in animals, in particular in mammals. The present invention also relates to such specific binding moieties, in particular to antibodies and/or to antigen binding fragments thereof, specifically binding to structurally disordered and/or intrinsically disordered sequences, in particular to Pro/Ala-rich sequences (PAS). These binding moieties, antibodies, antigen binding fragments are first in class since they bind to/recognize disordered peptides or polypeptide fragments as also comprised in such “intrinsically disordered proteins”, in particular PAS polypeptides. The inventive binding moieties, antibodies, antigen binding fragments are, without being limiting, particularly useful in diagnostic settings as well as research tools.