Chymase-Binding Aptamer Sequence and Stem-Loop Structure
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Solution Overview
Problem
Current chymase inhibitors are inadequate in effectively addressing fibrosis and related diseases, as the mechanism of fibrosis at the molecular level is not well elucidated, and existing treatments do not fully inhibit chymase activity.
Innovation Solution
Development of an aptamer with a specific nucleotide sequence and secondary structure that binds to chymase, inhibiting its activity, which is more effective than previously reported aptamers, with a potential sequence represented by UAACR1N1R2GGGG and a stem-loop partial structure, capable of binding to chymase and inhibiting its enzyme activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing chymase inhibitors are used, then chymase activity is partially inhibited, but the inhibitory effectiveness is insufficient for treating fibrosis and related diseases
Solution Approach 1:
The patent applies parameter changes by optimizing the aptamer sequence (UAACR1N1R2GGGG) and secondary structure (stem-loop) to achieve superior binding affinity and inhibitory activity. The specific nucleotide sequence and structural conformation were refined to produce an aptamer with IC50 values as low as 1 nM, dramatically improving therapeutic efficacy compared to existing inhibitors.
Solution Approach 2:
The patent uses copying by creating an aptamer that mimics the binding characteristics of traditional inhibitors but with enhanced potency. The aptamer replicates the inhibition function while achieving superior effectiveness through its unique nucleotide sequence and stem-loop structure, thereby overcoming the limitations of conventional chymase inhibitors.
2Reliability
If existing aptamers are used, then some chymase inhibition is achieved, but the inhibitory activity is significantly lower than required for effective treatment
Solution Approach 1:
The patent applies parameter changes by precisely optimizing the aptamer's nucleotide sequence (UAACR1N1R2GGGG) and secondary structure to achieve IC50 values as low as 1 nM. This level of precision in molecular design enables the aptamer to bind chymase with extremely high affinity, far surpassing the inhibitory activity of previously reported aptamers.
Solution Approach 2:
The patent applies segmentation by dividing the aptamer into functional segments: the specific nucleotide sequence (UAACR1N1R2GGGG) that provides binding specificity and the stem-loop secondary structure that stabilizes the binding conformation. This segmentation allows each component to be optimized independently for maximum inhibitory activity.
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 aptamer demonstrates significantly higher inhibitory activity against chymase, with IC50 values as low as 1 nM, compared to previously reported aptamers, offering a more effective therapeutic option for fibrosis and cardiovascular diseases by specifically targeting and inhibiting chymase activity.
Implementation Method 1
An aptamer that binds to chymase, and comprises a common sequence represented by UAACR1N1R2GGGG wherein R1 and R2 are each any one base, and N1 shows 3 to 30 bases (uracil is optionally thymine)
Data Source
AI summary
The present invention provides an aptamer that binds to chymase, and contains a common sequence represented by UAACR1N1R2GGGG wherein R1 and R2 are each any one base, and N1 shows 3 to 30 bases (uracil is optionally thymine).