Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12398174-B2
Publication Date
2025-08-26
Expiration Date
Abstract
Compositions and methods for optically-verified, sequence-controlled polymer synthesis are described.
Core Innovation
Optically verified, sequence-controlled polymer/oligomer synthesis is performed using monomer units that include removable, fluorescently-labeled protecting or blocking groups. Each addition step is carried out with an immobilized seed/template, and fluorescence detection confirms the status of the corresponding protecting/blocking label before it is removed to enable the next iterative addition.
The synthesis supports template-free iterative chemistries in which monomer units bearing fluorescently-labeled removable protecting groups participate in repeated coupling, and the fluorescently-labeled protecting group is removed after fluorescence verification. The disclosed variants include approaches based on boronate analogs and silyl groups, including silyl analogs, with the labeled groups used to validate addition during sequence-controlled polymer growth.
DNA-templated synthesis is also disclosed, where single-stranded DNA seeds are immobilized and fluorescently-labeled peptide nucleic acid (PNA)-coupled macrocycle monomer units are hybridized to the seed for iterative sequence building. Hybridization is fluorescence-validated, and the macrocycle/PNA linkage includes disulfide bonds that are cleaved to release the final oligomer or sequence-specific PNA polymer chain.
A fluorescence-based measurement concept is additionally disclosed using FRET between donor and acceptor fluorophores to measure inter-unit distances during synthesis, including the ability to diagnose stalling or termination. The document also describes using removable fluorescent label/linker elements coupled through fluorophore-cleavable linkers and repeating fluorescence-verified cycles to maintain sequence control.
Claims Coverage
Two independent claim groupings are identified. Across the independents, the claims emphasize disulfide-bonded PNA-coupled macrocycles and removable fluorescently-labeled protecting groups that provide fluorescence-validated sequence control, including both structural monomer definitions and fluorescence-based verification during iterative addition.
Bifunctional building block with removable fluorescently-labeled protecting group forming a macrocycle via PNA disulfide coupling
A bifunctional building block coupled to a peptide nucleic acid (PNA) through disulfide bonds to form a macrocycle, wherein the protecting group comprises a boronate analog, a silyl group, or a silyl analog, and wherein the bifunctional building block comprises a removable, fluorescently-labeled protecting group.
Fluorescently-labeled macrocycle monomer unit formed by PNA-disulfide coupling with optional removable protecting group
A monomer unit comprising a bifunctional building block coupled to a peptide nucleic acid (PNA) through disulfide bonds to form a macrocycle, wherein the macrocycle is fluorescently-labeled, and optionally wherein the bifunctional building block comprises a removable protecting group, and the protecting group comprises a boronate analog, a silyl group, or a silyl analog.
The claim coverage centers on monomer units that form a macrocycle by coupling a bifunctional building block to PNA through disulfide bonds, with fluorescence introduced either via removable fluorescently-labeled protecting groups or by making the macrocycle fluorescently labeled. The disclosed claim set further associates these monomers with fluorescence-verified iterative sequence control, including DNA-templated hybridization using a fluorescently labeled PNA-coupled macrocycle monomer unit and, optionally, disulfide cleavage to release the sequence-specific polymer chain.
Stated Advantages
Optical verification of each sequence-controlled addition step by fluorescence detection before removal of the protecting or blocking label for the next cycle.
Supports sequence-controlled synthesis, including DNA-templated iterative sequence building with fluorescence-validated hybridization.
FRET-based distance measurement concept to diagnose stalling or termination during synthesis.
Documented Applications
Optically verified, sequence-controlled polymer or oligomer synthesis using iterative addition on an immobilized seed or template.
Template-free iterative chemistries using monomer units with removable fluorescently-labeled protecting groups, with fluorescence used to confirm each step before label removal.
DNA-templated synthesis with an immobilized single-stranded DNA seed, where fluorescence detection verifies hybridization of fluorescently-labeled PNA-coupled macrocycle monomer units and iterative sequence building is performed.
Measuring inter-unit distances during synthesis using FRET between donor and acceptor fluorophores to diagnose stalling or termination.
Interested in licensing this patent?