Recombinant Fyn SH3 Binding Proteins for Intracellular Targeting
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Solution Overview
Problem
Current binding molecules, such as monoclonal antibodies, have limitations in terms of biophysical properties and immunogenicity, making them less suitable for therapeutic and diagnostic applications, especially for intracellular targets which are prone to eliciting immune responses.
Innovation Solution
Development of recombinant binding proteins derived from the SH3 domain of the Fyn kinase, specifically mutated in the RT and src loops to enhance target specificity and affinity, while maintaining high sequence identity to the native SH3 domain, thereby minimizing immunogenicity and improving stability and solubility under physiological conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monoclonal antibodies are used as binding molecules, then high affinity and specificity to targets can be achieved, but immunogenicity increases and biophysical properties are limited
Solution Approach 1:
The patent creates simplified copying versions of the antibody binding function using SH3 domains. Instead of using full immunoglobulin structures, the invention copies only the essential binding capability through smaller protein scaffolds (SH3 domains) that can be engineered to recognize specific targets while lacking the immunogenic components of complete antibodies.
Solution Approach 2:
The patent employs smaller, simpler binding proteins (SH3 domains) that function as disposable or temporary binding agents. These compact proteins provide the necessary binding function without the complexity and immunogenicity of full antibodies, making them suitable for applications where prolonged exposure might trigger immune responses.
2Adaptability or versatility
If binding molecules are used for intracellular targets, then therapeutic and diagnostic applications are enabled, but immune responses are elicited due to immunogenicity
Solution Approach 1:
The invention creates simplified copies of antibody binding function using SH3 domains that can access intracellular targets. These copied binding functions are embedded in smaller protein structures that are less immunogenic, enabling intracellular targeting applications without triggering strong immune responses that would occur with full antibodies.
Solution Approach 2:
The patent changes the fundamental parameters of the binding molecule - using SH3 domains instead of complete antibodies. This parameter change reduces molecular size, complexity, and immunogenicity while maintaining binding functionality, thereby enabling applications in intracellular environments where full antibodies would be problematic.
3Object-affected harmful factors
If SH3 domains are used as binding proteins, then immunogenicity is reduced and stability is improved, but binding affinity and specificity must be engineered through mutations
Solution Approach 1:
The patent applies local quality changes by introducing specific mutations in the RT and n-Src loops of the SH3 domain. These localized modifications in critical binding regions enhance target recognition and affinity without altering the overall stable structure of the SH3 domain, thereby maintaining low immunogenicity while improving binding properties.
Solution Approach 2:
The invention systematically changes amino acid parameters in the SH3 domain loops to optimize binding properties. By modifying specific residues in the RT and n-Src loops, the patent tunes the binding affinity and specificity while preserving the core structural stability and low immunogenicity characteristics of the SH3 domain scaffold.
Data Source
AI summary
The present invention relates to a method for the production of a library comprising recombinant derivatives of the SH3 domain of the Fyn kinase of SEQ ID NO: 1 as well as a method for selecting from a library comprising recombinant derivatives of the SH3 domain of the Fyn kinase of SEQ ID NO: 1 one or more of said derivatives having a specific binding affinity to a protein or peptide.