Linear Initiator Nucleic Acids for Bivalent Molecule Synthesis
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Solution Overview
Problem
Existing methods struggle to detect interactions between library compounds and target molecules when interactions are present in low numbers or when library compounds are present in low numbers, necessitating improved libraries and synthesis methods.
Innovation Solution
The method involves preparing linear initiator nucleic acids by cleaving a circularized nucleic acid to form a linear initiator nucleic acid, which comprises a first and second initial building block attached to opposite ends of a coding region, allowing for the synthesis of bivalent molecules that enhance reactivity and target binding during compound analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If existing library synthesis methods are used, then compounds can be prepared in a single process, but interactions between library compounds and target molecules cannot be detected when present in low numbers
Solution Approach 1:
The patent combines multiple building blocks (first initial building block, second initial building block, and polymer building blocks) onto a single nucleic acid scaffold to create bivalent molecules. This merging approach increases the number of binding sites per molecule, thereby enhancing the detectability of interactions even when target molecules are present in low numbers.
2Quantity of substance
If existing library synthesis methods are used, then combinatorial libraries can be synthesized, but the library compounds themselves are present in low numbers making detection difficult
Solution Approach 1:
The patent changes the valency parameter of the library compounds from monovalent to bivalent by incorporating two different initial building blocks that can each bind to target molecules. This parameter change increases the binding capacity and detection sensitivity of each compound in the library.
3Measurement precision
If bivalent molecules are synthesized, then sensitivity of assays is increased, but the synthesis process becomes more complex
Solution Approach 1:
The patent employs self-service principles through the use of encoded synthesis methods where the nucleic acid sequence itself directs the assembly of building blocks. The coding region encodes the specific sequence of building block additions, allowing the system to automatically guide the synthesis process without requiring complex external control mechanisms.
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
Bivalent molecules increase the sensitivity of assays, enabling the identification of both strong and moderate binders for target proteins, thereby improving the efficiency of compound screening and refining candidates with weak affinities.
Implementation Method 1
the cleavage is by enzymatic cleavage. In some embodiments, the enzymatic cleavage is by restriction digestion
Data Source
AI summary
The present disclosure relates to bivalent or polyvalent linear initiator nucleic acids comprising initial building blocks and a coding region. The linear initiator nucleic acids may be used for the synthesis of an encoded compound to produce bivalent or polyvalent molecules.