2′3′-Cyclic Phosphonate Dinucleotides for STING Activation
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Solution Overview
Problem
Current cyclic dinucleotides used to activate the STING adaptor protein are susceptible to hydrolysis by phosphodiesterases in tissues and bodily fluids, limiting their effectiveness as anti-viral, anti-cancer agents and vaccine adjuvants.
Innovation Solution
Development of novel 2′3′-cyclic phosphonate dinucleotides with phosphonoalkyl groups that are resistant to hydrolysis, capable of binding and activating the STING protein to induce interferons and cytokines, thereby treating viral infections, cancers, and inflammatory diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current cyclic dinucleotides are used to activate STING adaptor protein, then immune response is induced, but stability in biological environments deteriorates due to hydrolysis by phosphodiesterases
Solution Approach 1:
The patent changes the chemical parameter of the cyclic dinucleotide by replacing the natural phosphodiester bond with a phosphonate bond. This parameter change confers resistance to hydrolysis by phosphodiesterases, thereby improving stability in biological environments while extending the duration of action of the compound
Solution Approach 2:
The patent creates a composite molecular structure by combining phosphonate groups with cyclic dinucleotide bases (such as 2′3′-cGAMP or 2′3′-cAMP). This composite structure maintains the biological activity of the original cyclic dinucleotide while adding hydrolysis resistance through the phosphonate linkage
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 novel 2′3′-cyclic phosphonate dinucleotides effectively activate the STING protein, leading to the production of interferons and cytokines, enhancing immune responses and providing therapeutic benefits for viral infections, cancers, and inflammatory conditions while maintaining stability in biological environments.
Implementation Method 1
novel 2′3′-cyclic phosphonate dinucleotides with phosphonoalkyl groups that are resistant to hydrolysis
Implementation Method 2
capable of binding and activating the STING protein to induce interferons and cytokines
Data Source
AI summary
The present disclosure relates to 2′3′-cyclic dinucleotides modified with a 2′- or 3′-phosphonoalkyl bond and derivatives thereof, that can modulate the activity of the STING adaptor protein.