Cysteine-Optimized Stradomers for Aggregation Control
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Recombinant anti-inflammatory and anti-autoimmune agents face challenges due to cysteine residues not involved in disulfide bond formation, which can lead to unwanted chemical modifications and aggregation, reducing the stability and functionality of stradomers.
Innovation Solution
Development of cysteine-optimized multimerizing stradomer units with point mutations at specific amino acid positions, reducing the number of cysteine residues while maintaining multimerization and function, thereby minimizing unwanted oxidation reactions and aggregation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cysteine residues are present in stradomers, then multimerization and function are maintained, but unwanted chemical modifications and aggregation occur
Solution Approach 1:
The patent removes problematic cysteine residues from the stradomer sequence while preserving the essential multimerization capability. Specific cysteines at positions 5, 11, 14, 152, 210, 237, 240, and 243 are eliminated through point mutations, extracting the harmful chemical reactivity while maintaining the functional core structure
Solution Approach 2:
The patent changes the amino acid composition parameters by substituting cysteine residues with alternative amino acids at specific positions. This parameter change reduces the chemical reactivity and aggregation propensity while preserving the multimerization function through careful selection of replacement residues
2Object-generated harmful factors
If cysteine residues are reduced in stradomers, then chemical modifications and aggregation are minimized, but multimerization and function may be reduced
Solution Approach 1:
The patent applies local quality by making site-specific modifications only at particular cysteine positions (5, 11, 14, 152, 210, 237, 240, 243) while leaving other regions intact. This localized approach eliminates harmful cysteines in aggregation-prone regions while preserving cysteines or structural features necessary for multimerization and biological function
3Stability of the object's composition
If point mutations are introduced at specific amino acid positions, then cysteine residues are reduced and stability is improved, but sequence complexity increases
Solution Approach 1:
The patent segments the cysteine elimination strategy into specific, discrete position targets (5, 11, 14, 152, 210, 237, 240, 243). Rather than attempting global cysteine removal, the approach divides the problem into manageable site-specific mutations, making the sequence design systematic and controllable
Data Source
Figure 1
Figure 2
Figure 3~4
AI summary
The present disclosure involves biologically active proteins termed cysteine-optimized multimerizing stradomers. Thus, the present disclosure provides compositions and methods providing anti-autoimmune and anti-inflammatory activities, useful in the treatment of diseases and conditions including autoimmune diseases, inflammatory diseases, or infectious diseases.