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Custom mono- and polyunsaturated fatty acid conjugation for DNA, RNA, ASO, siRNA, duplex RNA and specialty oligonucleotides, including oleic acid, linoleic acid, α-linolenic acid, arachidonic acid, EPA, DPA and DHA architectures with terminal, internal and multivalent design options.
Unsaturated fatty acid-modified oligonucleotides combine hydrophobic lipid character with one or more carbon-carbon double bonds. Compared with saturated analogs of similar chain length, unsaturation can alter chain flexibility, molecular packing, membrane interaction, protein association, self-assembly, chromatographic retention, and formulation behavior.
Bio-Synthesis can evaluate terminal, selected internal, mono-lipid, dual-lipid, and multivalent unsaturated fatty acid architectures. The final design should define fatty acid identity, double-bond pattern, position, linker, valency, oligonucleotide modality, and analytical strategy together.
Representative architecture: the DHA figure shows how one highly unsaturated lipid can be presented as mono-, di-, or multivalent oligonucleotide conjugates. DHA is an example; the page covers a broader MUFA and PUFA design space.
Representative mono-, di- and multivalent DHA-oligonucleotide architectures
C14-C24 research-relevant unsaturated fatty acids provide a broad hydrophobic design space.
One or multiple double bonds can substantially alter conformation and physicochemical behavior.
5′, 3′ and selected internal attachment can be evaluated through suitable conjugation or custom direct chemistry.
Single-, dual- and multivalent architectures allow systematic comparison of lipid number and presentation.
The library is organized by carbon number and degree of unsaturation. Exact cis/trans geometry, omega family, and double-bond position should be specified when they matter to the intended construct or study.
Monounsaturated fatty acid
5′ • 3′ • selected internal
cis-C18:1; common MUFA reference
Positional C18:1 isomer
n-6 PUFA
n-3 PUFA
Monounsaturated C20 fatty acid
C20 PUFA
n-9 PUFA
n-3 long-chain PUFA
Very-long-chain MUFA
n-3 or n-6 isomer should be specified
n-3 highly unsaturated PUFA
5′ • 3′ • selected internal • multivalent
Availability note: this is a research-relevant library, not a claim that every lipid exists as a routine off-the-shelf phosphoramidite. Post-conjugation is the broadest route; direct-incorporation chemistry is project specific unless a validated reagent is available.
Matched-chain lipid series can help separate the effect of carbon-chain length from the effect of double-bond number. C18 is a useful example because saturated and progressively unsaturated analogs can be compared within the same carbon count.
Stearic Acid
Oleic Acid
Linoleic Acid
ALA / GLA
Design use: a C18:0 → C18:1 → C18:2 → C18:3 series can be used to investigate how increasing unsaturation changes oligonucleotide conjugate behavior while keeping the overall carbon count similar.
Oleic, linoleic, ARA, EPA and DHA conjugates can be evaluated as hydrophobic siRNA architectures for cellular association, tissue-exposure and delivery research.
Unsaturated fatty acids can be combined with antisense backbones to study protein association, cellular uptake, distribution and hydrophobicity.
Unsaturated lipid anchors can be explored for membrane association, cell-surface presentation, and lipid-rich model systems.
Compare chain length, unsaturation, omega family, position and valency while keeping the oligonucleotide sequence fixed.
Unsaturated fatty acids can be combined with fluorophores or reporters when linker and label placement are designed to minimize interference.
Unsaturated lipid-oligo conjugates can be evaluated in lipid-rich assemblies, model nanoparticles or multicomponent delivery systems.
Keep carbon count similar while increasing double bonds.
Hold unsaturation class relatively constant while changing lipid length.
Compare biologically distinct unsaturated lipid families.
Separate lipid identity from presentation on the oligonucleotide.
The oligonucleotide is first synthesized with a reactive handle and then coupled to an activated unsaturated fatty acid or lipid derivative.
Best fit: broad lipid screening, custom spacers, internal handles, and multivalent constructs.
A dedicated modifier or phosphoramidite may be developed when the desired linkage and position justify a direct solid-phase synthesis route.
Best fit: repeated programs where the exact modifier architecture is already defined.
Multiple unsaturated fatty acid groups can be presented through branched scaffolds or orthogonal attachment handles.
Watch: hydrophobicity, conversion, purification, aggregation and analytical homogeneity.
Terminal or selected internal unsaturated fatty acid conjugation for specialty DNA, probes and membrane-association studies.
Terminal or selected internal lipidation with attention to deprotection, handling and oxidation-sensitive chemistry.
Unsaturated lipid conjugation can be coordinated with PS and affinity-enhancing sugar-modified antisense architectures.
Evaluate strand, terminus, linker, valency and stabilization pattern together with lipid identity.
Hydrophobic anchors can support membrane association or formulation studies while preserving folding and binding.
Lipid and fluorophore placement should be separated enough to reduce steric or optical interference.
Multiple attachment points enable comparative mono-, di- and multivalent unsaturated lipid architectures.
Customer-supplied lipids, defined isomers and multicomponent architectures can be reviewed for feasibility.
Omega-3 fatty acids form an important specialty subset of the unsaturated-fatty-acid platform. ALA, SDA, EPA, DPA and DHA differ in chain length and degree of unsaturation and can support distinct oligonucleotide conjugation studies.
Dedicated subpage planned: use the Omega-3 Oligonucleotide Conjugates page for deeper EPA/DPA/DHA application, stability, and design guidance.
Carbon-carbon double bonds increase susceptibility to oxidative degradation. This concern generally becomes more important as the number of double bonds increases, particularly for highly polyunsaturated EPA- and DHA-containing constructs.
C18:1
C18:2
C20:4
C20:5
C22:6
Minimize unnecessary exposure during storage and handling, especially for highly polyunsaturated constructs.
Low-temperature storage may be appropriate depending on formulation, sequence and final product format.
Unsaturated conjugates can show different chromatographic behavior from saturated analogs of similar chain length.
Mass and chromatographic profiles should be reviewed for the intended conjugate and degradation-related species when relevant.
Expected molecular mass and conjugate assignment by an appropriate mass method.
RP-HPLC or other fit-for-purpose chromatography adapted to hydrophobicity and lipid structure.
Assessment of conversion and separation from unconjugated oligo or excess lipid-related species.
Project-specific attention to oxidative stability for highly unsaturated constructs.
Annealing and duplex assessment for siRNA or other duplex RNA designs when required.
C4-C22 saturated fatty acid conjugation, direct modifier chemistry, 3′ supports, and 2′-O-C16/C22 architectures.
Broader lipid-conjugation platform covering fatty acids, sterols, phospholipids, PEG-lipids and other hydrophobic modifiers.
Project-specific conjugation of oligonucleotides to lipids, peptides, proteins, dyes, small molecules and other functional groups.
Custom siRNA design and manufacturing for modified, conjugated and specialty RNAi architectures.
Custom terminal and internal reactive handles for post-synthetic coupling, click chemistry and branched architectures.
Dedicated ALA, SDA, EPA, DPA and DHA conjugation platform for deeper omega-3 design and application guidance.
Lipid: Oleic, Linoleic, ALA, ARA, EPA, DPA, DHA, other Isomer: cis/trans, n-3/n-6/n-9 where relevant Position: 5′, 3′, internal Valency: 1×, 2×, multivalent Oligo: DNA, RNA, ASO, siRNA
Ask about matched lipid series by chain length, degree of unsaturation, omega family, attachment position or valency.
Custom unsaturated fatty acid-modified oligonucleotides are supported by documented synthesis or conjugation, purification, analytical QC, traceability and project-specific handling from feasibility through repeat manufacturing.
These publications focus on hydrophobic and fatty-acid conjugation of siRNA and related oligonucleotide architectures, including DHA, EPA, saturated and unsaturated fatty acids, lipid valency, systemic distribution, and extrahepatic delivery.
Scientific note: these studies illustrate design principles rather than a universal ranking of lipids. Unsaturated fatty acid identity, chain length, double-bond pattern, position, linker, valency, oligonucleotide chemistry, and route of administration can all influence the behavior of the final conjugate.
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