Quasirandom Synthesis Using Connector Polynucleotides
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Solution Overview
Problem
Existing methods for synthesizing molecules, such as template directed synthesis, are limited in generating large libraries of molecules due to their deterministic nature and inability to predict the final structure of supramolecular complexes, and they often require a high number of anti-codons or transfer units, limiting variability and flexibility.
Innovation Solution
The method involves using connector polynucleotides (CPNs) that guide the synthesis of molecules by hybridizing with complementary connector polynucleotides (CCPNs) harboring reactive groups, allowing for the formation of supramolecular hybridization complexes where functional entities can be transferred and reacted to form covalently linked molecules without the CPNs or CCPNs being covalently linked, enabling a quasirandom structure and function-guided synthesis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If template directed synthesis methods are used, then the synthesis process is deterministic and structured, but the ability to generate large libraries with high variability is limited
Solution Approach 1:
The system segments the synthesis process into modular components: CPNs serve as programmable scaffolds that can be independently designed and combined, while CCPNs carrying functional entities act as separate reagent modules. This segmentation allows combinatorial assembly of large molecule libraries without requiring proportionally large numbers of unique transfer units, as the CPN framework provides structural organization.
Solution Approach 2:
CPNs act as intermediary structures that mediate between the information-carrying polynucleotide sequence and the chemical functional entities. The CPN framework serves as a programmable scaffold that organizes and presents functional entities in controlled geometries, enabling library diversity through sequence variation rather than requiring diverse transfer unit assemblies.
2Productivity
If multiple reactive groups are reacted to generate molecules, then functional entities can be covalently linked, but the donor CCPNs become covalently linked and cannot be reused
Solution Approach 1:
The system extracts the functional entity from its original CCPN context and transfers it to a new molecular framework. The donor CCPN's functional entity is separated and incorporated into the growing molecule structure, while the donor CCPN itself remains intact and available for further reactions. This extraction approach allows reusable donor pools to generate diverse molecular libraries.
Solution Approach 2:
The donor CCPNs are effectively discarded as single-use carriers after donating their functional entities, but the system recovers value by using the same donor pool repeatedly across multiple synthesis cycles. The functional entities are transferred and incorporated into final molecules, while the donor CCPNs can be replenished or recycled in the system.
3Adaptability or versatility
If template directed synthesis is used, then the process follows a fixed sequence, but flexibility in synthesizing diverse chemical compounds is reduced
Solution Approach 1:
The system introduces dynamic reactivity through multiple reactive group types that can be selectively activated. Different reactive groups on CCPNs can undergo different chemical transformations depending on conditions, allowing the same CPN framework to direct diverse synthesis pathways. This dynamic chemical behavior provides flexibility without requiring complex reprogramming of the polynucleotide sequences.
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
This approach allows for high reactivity, controllable reactant reactivity, and efficient selection of desirable molecules, enabling the generation of large libraries with high variability and flexibility, including the ability to evolve scaffolds and attachments, and reduces the need for extensive anti-codons or transfer units, resulting in cost-effective synthesis of diverse chemical compounds.
Implementation Method 1
connector polynucleotides (CPNs) capable of hybridizing to complementary connector polynucleotides (CCPNs)
Data Source
AI summary
The present invention is directed to the synthesis of molecules guided by connector polynucleotides (CPNs) capable of hybridizing to complementary connector polynucleotides (CCPNs) harboring at least one functional entity comprising at least one reactive group. At least one of the CCPNs is capable of hybridizing to at least two CPNs. Each CPN will “call” for one or more CCPNs capable of hybridization to the CPN. Following the formation of a supramolecular hybridization complex comprising a plurality of CPNs and a plurality of CCPNs, the reaction of reactive groups results in the formation of a molecule comprising covalently linked functional entities. The formation of the molecule involves the transfer of functional entities from one or more “donor CCPNs” to at least one “acceptor CCPN” with which the transferred functional entities were not associated prior to the transfer.