Methods and materials for discovery of functional ligands to molecular complexes
Inventors
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Assignees
Member
Base Pair BiotechnologiesBase Pair Biotechnologies specializes in custom aptamer discovery and development for research, diagnostics, therapeutics, and industrial applications. The company leverages proprietary multiplex selection, advanced bioinformatics, and chemical modification techniques to develop high-affinity and selective nucleic acid aptamers. Base Pair enables affinity reagent development, biosensor design, and molecular detection for a broad range of targets and partners across academia and industry.
Base Pair Biotechnologies specializes in custom aptamer discovery and development for research, diagnostics, therapeutics, and industrial applications. The company leverages proprietary multiplex selection, advanced bioinformatics, and chemical modification techniques to develop high-affinity and selective nucleic acid aptamers. Base Pair enables affinity reagent development, biosensor design, and molecular detection for a broad range of targets and partners across academia and industry.
Publication Number
US-12338434-B1
Publication Date
2025-06-24
Expiration Date
Abstract
This invention relates to methods and materials for discovery of functional ligands, particularly to methods and materials for selecting for functional ligands to molecular complexes, and more particularly to methods and materials for selecting for functional ligands to molecular complexes with metal ions, such as coordination complexes with metal ions. For example, functional ligands, such as aptamers, may be selected for specific and high affinity binding to coordination complexes of metal ions of interest, such as particular arsenic ions.
Core Innovation
This invention relates to methods and materials for discovery of functional ligands, particularly to methods and materials for selecting for functional ligands to molecular complexes, and more particularly to methods and materials for selecting for functional ligands to molecular complexes with metal ions, such as coordination complexes with metal ions. Functional ligands, such as aptamers, may be selected for specific and high affinity binding to coordination complexes of metal ions of interest, such as particular arsenic ions. Functional ligands may generally include biomolecules such as nucleic acids, such as single-stranded nucleic acids and double-stranded nucleic acids or combinations or regions of both, peptides, other biopolymers and/or combinations or modifications thereof, such as artificially modified nucleic acids, synthetic analogs and the like.
Small molecular or ionic targets, such as metal ions, may present difficulties for discovering functional ligands with sufficient specificity to discriminate between the target and other small molecular or ionic species, and generating directly binding functional ligands which may bind at an appropriate affinity. Many chelating or other complexing agents exist which may display significant specificity to particular ions and may themselves present as targets for selecting functional ligands when in the context of binding particular ions or in the context of not binding the desired ions. In some exemplary embodiments, functional ligands may be selected against targets that include a complexing agent specific and/or semi-specific to a desired ionic species bound and unbound to said ionic species, for example, simultaneously, sequentially or in parallel, such that functional ligands that bind to both the bound and unbound complexing agent may be eliminated and/or otherwise designated as non-specific to one or the other.
Claims Coverage
The independent claim recites four main inventive features.
Library of biomolecules
Providing a library of biomolecules.
Arsenic(III) coordination complex target
Contacting said library with a target, said target comprising a target ionic species comprising arsenic (III) ion complexed with a coordination compound selected from the group consisting of 4-(mercaptomethyl)benzoic acid, 1,4-benzenedimethanethiol, meso-2,3-dimercaptosuccinic acid, 2,3-dimercapto-1-propanesulfonic acid, and 2,3-dimercapto-1-propanol.
Sequestering binders by non-Watson-Crick non-covalent binding
Sequestering members of said library which bind to said target, wherein said members bind via non-Watson-Crick and non-covalent binding.
Determination of composition or sequence
Determining the composition or sequence of said members which bind to said target.
Claim 1 covers providing a biomolecular library, contacting it with an arsenic(III) coordination complex chosen from a specified group of coordination compounds, sequestering binders that engage via non-Watson-Crick and non-covalent binding, and determining the composition or sequence of those binders.
Stated Advantages
Selection or discovery of functional ligands capable of specific and high affinity binding to coordination complexes of metal ions, such as arsenic ions.
Ability to select functional ligands that discriminate between bound and unbound complexing agents and between complexes with desired versus undesired ionic species or valence states.
Utility of functional ligands for detection, quantification, and other diagnostic applications, including detecting ionic species in fluids.
Use in detection formats such as lateral flow assays using the functional ligands as the detection agent and fluorescence assays with aptamer beacons that change conformation upon binding to their target.
Documented Applications
Detection, quantification, and other diagnostic applications for ionic species in fluids.
Detecting contamination in water sources.
Lateral flow assays using the functional ligands as the detection agent.
Fluorescence assays with functional ligands formed as aptamer beacons which change conformation upon binding to their target.
Use of aptamers as sensors, therapeutic tools, to regulate cellular processes, and to guide drugs to their specific cellular target(s).
Immobilized capture elements in a microarray format.
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