Oligosaccharide analytical standards
Inventors
Boons, Geert-Jan • Prudden, Anthony Robert • Liu, Lin
Assignees
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Publication Number
US-12152053-B2
Publication Date
2024-11-26
Expiration Date
Abstract
Disclosed herein are oligosaccharides and intermediates useful for the production thereof. The compounds are useful as analytical standards and as intermediates for the preparation of more complex oligosaccharide and N-glycan products. The compounds may be prepared in high purity using the selective stop/go synthetic methods disclosed herein.
Core Innovation
The patent relates to a compound represented by a specified structural formula, or a pharmaceutically acceptable salt thereof. The compounds are defined by extensive substituent variability at multiple positions, including R1, Rfa, R2, R4, R5, R6, R7, R8, R12, R13, R14, R15, R16, R17, R18, and R19-20, using residues and optional functional groups such as OH and amine-containing options. The framework includes an optional fucose residue at Rfa and multiple substituent patterns constrained by explicit residue formulas and Z—X definitions.
The disclosure includes glycan-containing and N-glycan analytical standard compounds and related oligosaccharides, with variable substituents such as H, GlcNAc, fucose, Gal, Neu5Ac, and defined residue formulas. It also defines azide- or substituted amine-containing residue patterns, including N3 or NR variants with Z—X substitution frameworks, and conjugated-payload-bearing moieties, including payload conjugation via click chemistry to triazole-linked moieties where Y is a cytotoxic drug or tracer and L is a linker that can be cleavable or non-cleavable.
The disclosed embodiments include complex N-linked oligosaccharide analytical standards and related intermediates, with temporary disabling of residues from further enzymatic extension based on stop/go logic and optional isotopic enrichment using labeled residues such as 13C-enriched residues. The structures also include tags and immobilization motifs such as fluorescent/UV-VIS/LC-MS/solid-phase tags and microarray-immobilization groups such as biotin and sulfonated aryl groups, with analytical use in methods such as mass spectrometry, HPLC, capillary electrophoresis, and NMR.
Claims Coverage
The claims coverage is centered on a structural-formula-defined compound, or a pharmaceutically acceptable salt, with numerous inventive structural features controlled by substituent definitions across multiple R-positions. The inventive features include the overall compound framework, optional fucose incorporation, constrained OR/NR and N3/Z—X substitution patterns, explicit OH/H assignments within defined residue substructures, and payload-bearing triazole-linked embodiments.
Structural formula compound with pharmaceutically acceptable salt
A compound represented by a specified structural formula, or a pharmaceutically acceptable salt thereof, with substituents at multiple positions defined by OH, hydrogen, or residue formulas.
Optional fucose residue at Rfa
Rfa is H or a fucose residue represented by a specified formula.
Functional group and linkage variability at R2
R2 is ORc, NR2nORc, or NR2aRc, where R2n is H or a C1-4 alkyl and Rc is H or a C1-8 alkyl.
N3 and N-containing substituent patterns at R4 and R5
R4 is N3 or NR4aR4b and R5 is N3 or NR5aR5b, where the subgroups are independently H or Z—X, with Z null, C(O), or SO2, and X C1-4 alkyl or C1-4 haloalkyl.
Residue-defined substituents at R6 and R7
R6 and R7 are hydrogen or residues represented by specified formulas, including N3 or NR9aR9b / NR10aR10b patterns with Z—X constraints.
Hydroxyl-patterned residue definitions at R13 through R20
R13, R14, R15, R16, R17, R18, and R19-20 are hydrogen or residue structures with explicit H and OH subpart assignments in the defined residues.
Payload-bearing triazole-linked moiety capability
Glycan or oligosaccharide embodiments include positions that can bear a conjugated payload, with payload conjugation via click chemistry to triazole-linked moieties where Y is a cytotoxic drug or tracer and L is a linker that can be cleavable or non-cleavable.
Coverage centers on a structurally defined compound, or pharmaceutically acceptable salt, with extensive position-dependent substituent definitions. The main inventive features are optional fucose incorporation, constrained OR/NR and N3-based substitution patterns, defined hydroxyl-bearing residue substructures at later positions, and payload-bearing triazole-linked embodiments.
Stated Advantages
The compounds are stated to allow controlled activity of GlcNAc-derived intermediates toward galactosyltransferases.
The disclosure provides characterization using natural isotopic abundance or 13C-enrichment at a GlcNAc residue.
High purity analytical standards are supported by isotopic enrichment using labeled residues such as 13C-enriched residues.
The compounds are described as useful for methods such as mass spectrometry, HPLC, capillary electrophoresis, and NMR.
Kits may include isolated compounds provided in vials, with options including lyophilized mixtures.
Documented Applications
Controlled activity of GlcNAc-derived intermediates toward galactosyltransferases such as B4GalT1 in connection with UDP-Gal.
Characterization using natural isotopic abundance or 13C-enrichment at a GlcNAc residue.
Analytical standards for methods such as mass spectrometry, HPLC, capillary electrophoresis, and NMR.
Quantification/characterization of oligosaccharides.
Microarray immobilization using biotin and sulfonated aryl groups.
Payload conjugation via click chemistry to triazole-linked moieties.
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