Login / Register Order My Items
Contact Us
800.227.0627
Contact Us Quote Order Login / Register
Sugar Chemistry

Sugar-Modified Bases for RNA Oligonucleotides

Custom sugar-modified oligonucleotides — 2′-OMe, 2′-F, LNA, MOE, UNA, FANA, and 4′-Thio — engineered for enhanced stability, nuclease resistance, and therapeutic performance

Overview

Bio-Synthesis provides a complete portfolio of sugar-modified nucleotides for custom DNA and RNA oligonucleotide synthesis. By tailoring the ribose/deoxyribose scaffold with chemistries such as 2′-O-methyl (2′-OMe), 2′-fluoro (2′-F), MOE, LNA/BNA, cEt, UNA, FANA, 4′-Thio, and stereochemical variants, we help researchers fine-tune stability, hybridization, nuclease resistance, and protein interactions.

2′-substitutions (2′-OMe, 2′-F, MOE) improve nuclease resistance and pharmacokinetics; locked and bridged sugars (LNA/BNA/cEt/ENA) boost binding affinity and potency; flexible analogs (UNA, TNA, GNA) introduce conformational freedom for structural biology and probe design. These edits can be combined with PS backbones, conjugates, or terminal caps to achieve the right balance of activity, safety, and durability.

Our services support projects from discovery through regulated production. We provide design guidance (e.g., gapmer ASO wings, siRNA duplex stabilization, mRNA/sgRNA immune-silencing), scalable synthesis (from nmol to multi-gram), and full analytical validation (HPLC, ESI-MS/MALDI, Tm profiling, endotoxin/moisture analysis). Whether your goal is therapeutic development, diagnostic probe design, or fundamental research, our team delivers high-quality, application-ready sugar-modified oligos.

Stability ↑ Potency ↑ Off-target ↓ PK/PD Tunable Serum Nuclease Resistance RNase H Strategy Aware siRNA / ASO Design

Popular Sugar Modified RNA

Sugar edits tune nuclease resistance, duplex Tm, protein interactions, and innate sensing. Common strategies include 2′-OMe/2′-F/MOE, conformational locks (LNA/BNA/cEt/ENA), and alternative frameworks (FANA, TMO, SNA). These sugar modified bases alter the ribose/deoxyribose scaffold of nucleotides. By changing the stereochemistry, flexibility, or electronic environment of the sugar moiety, one can dramatically affect hybridization, nuclease resistance, and affinity for proteins such as RNase H, polymerases, or RISC components.

Hide Table and Notes
Product/Modification Function Applications Notes / Code
2′-O-Methyl (A, C, G, U) Stability ↑; innate sensing ↓. siRNA/ASO wings, mRNA mimicry, probes. Tm ↑ [2′OMe-A/C/G/U]
5-Propynyl-2′-OMe-U Affinity ↑; duplex Tm ↑. qPCR, beacons, antisense probes. Affinity ↑ [5-Pr-2′OMe-U]
Amino-2′-OMe-U/C Amine handle, solubility ↑. NHS-ester labeling, conjugation/LNP. Conjugation [2′OMe-NH₂-U/C]
2′-OMe-5-Me-U Stacking/recognition ↑. Stability tuning; base-analog studies. Tm ↑ [2′OMe-5-Me-U]
2′-OMe-Inosine Wobble/universal pairing. SNP detection; universal sites. Universal [2′OMe-I]
5-Iodo-2′-OMe-U Halogen for X-ray/UV crosslink. Structural probes; hybrid oligos. Halogen [5-I-2′OMe-U]
5-Bromo-2′-OMe-U As above; crystallography. Antisense; photo-work. Halogen [5-Br-2′OMe-U]
7-Deaza-2′-OMe-A/G Hoogsteen suppressed; selectivity ↑. Aptamers; siRNA design. Selectivity [7-deaza-2′OMe-A/G]
5-Me-2′-OMe-C Duplex formation ↑; immune ↓. Immune-silent designs. Immune ↓ [2′OMe-5-Me-C]
2′-OMe-2,6-Diaminopurine Triple H-bond to U. Duplex stabilization. Triple H-bond [2′OMe-DAP]
MOE (2′-O-methoxyethyl) Affinity ↑; PK/immune favorable. ASO wings; therapeutics. Tm ↑ [MOE-A/C/G/U]
2′-Fluoro (A/C/G/U/I) Rigidifies ribose; nuclease ↑. siRNA, gapmers, antivirals, NGS. Tm ↑ [2′F-N]
LNA / BNA / cEt / ENA Locked/bridged sugars; strong affinity. ASO wings; probe tips. Tm ↑↑ [LNA|BNA|cEt|ENA]
FANA Arabino-2′-F framework. Therapeutic/diagnostic oligos. Tm ↑ [FANA-N]
TMO / SNA / TNA / GNA Non-natural backbones/sugars. Nuclease-resistant designs; XNAs. XNA [TMO|SNA|TNA|GNA]
2′-O-Propargyl / 2′-O-Allyl Clickable/alkenyl handles. Post-synthetic conjugation. Clickable [2′O-Prop|2′O-All]
Technical Notes
  • Balance modification density: Too much stabilization (e.g., high LNA content) may block RNase H or reduce activity.
  • Mix-and-match chemistry: 2′-OMe + 2′-F or LNA gapmers often yield optimal stability + activity balance.
  • Application-driven design:
    • Therapeutics (siRNA, ASO): prioritize stability + RNase H compatibility.
    • Diagnostics/probes: prioritize affinity + signal (e.g., LNA for qPCR).
    • Structural biology: UNA/TNA for flexibility studies.
  • Toxicity & immune profile: Certain locked analogs (LNA, cEt) improve safety over phosphorothioates alone.

Speak to Scientist

2′-Deoxy Sugar Variants

Deoxy + stereochemical variants for stability and design, 2′-deoxy sugar edits (2′-F-dN, ara-dN, 2′-amino) modulate duplex geometry and nuclease sensitivity; dI provides wobble/degenerate pairing.

Show Products and Notes
Product/Modification Function Applications Notes / Code
2′-Deoxy-2′-Fluoro-dA/C/G/U Thermal & enzymatic stability ↑. Antisense/probes; hybrid studies. Tm ↑ [2′F-dN]
2′-Deoxy-arabinonucleic acids (ara-dN) Alternative stereochemistry. Cross-linking/antisense research. Ara [ara-dN]
2′-Deoxy-2′-Amino RNA Duplex stability ↑. Stability-tuned constructs. Tm ↑ [2′NH₂-RNA]
2′-Deoxy-Inosine (dI) Universal/wobble base. Degenerate primers; probes. Universal [dI]
L-DNA base Mirror chirality; nuclease-insensitive. Spiegelmer/chirality studies. Nuclease ↓ [L-DNA]
Technical Notes
  • 2′-F-dN raises Tm in hybrids and resists nucleases; mixing with RNA affects geometry.
  • dI lowers specificity; place strategically for variant coverage.

Speak to Scientist

Bridged & Locked Nucleic Acids

Constrained sugar rings for high affinity, LNA/BNA and related bridged systems constrain the ribose (C2′–O/C4′), delivering large per-residue Tm gains and potent binding—ideal for short probes and ASO wings.

Show Products and Notes
Product/Modification Function Applications Notes / Code
LNA (Locked Nucleic Acid) Affinity & Tm ↑↑. ASO/siRNA wings; diagnostics. Tm ↑↑ [LNA]
BNA (Bridged Nucleic Acid) LNA-like; high specificity. Antisense; miRNA work. Specificity [BNA]
cEt (Locked Ribose Nucleic Acid) LNA-like; high specificity. ASO wings in gapmers (potency ↑), splice-modulation steric-blockers, and short probes. Specificity [cEt]
ENA (Bridged Nucleic Acid) LNA-like; Excellent stabilization; validate Tm empirically; blend with 2′-OMe/MOE to fine-tune specificity/toxicity Antisense; high-affinity pobes. Specificity [ENA]
α-L-LNA (alpha-L) Enantiomeric LNA; selectivity. High-stringency probes. Chiral [α-L-LNA]
β-L-DNA Chiral DNA variant. Biophysical/diagnostic probes. Chiral [β-L-DNA]
Technical Notes
  • Affinity & Tm: LNA/BNA yield large per-base Tm increases (+2–8 °C). Use sparingly to avoid off-target effects.
  • Placement: For gapmers, keep 3–5 LNA/cEt residues per wing around a DNA gap (8–10 nt). Avoid locked bases inside the RNase-H core. For siRNA, 1–2 terminal LNAs per strand can improve stability.
  • Steric-block designs: Fully modified LNA/MOE backbones are compatible and highly stable.
  • Chirality variants: α-L-LNA and β-L-DNA offer unique specificity and can reduce protein binding.
  • Backbone context: Use PS backbones for serum stability; mix PS/PO to tune clearance.
  • Toxicity: Dense LNA runs can increase hepatotoxicity—blend with 2′-OMe/2′-F/MOE to mitigate.
  • Synthesis & QC: LNA/cEt amidites need slightly longer coupling. Verify Tm empirically; predictive models may underestimate.
  • Applications: Gapmer ASOs, splice modulation, short qPCR probes, siRNA stabilization, chiral probe design.
Speak to Scientist

Flexible & Acyclic Sugar Analogs

Tuning flexibility and geometry (UNA, GNA, HNA, CeNA). These frameworks adjust backbone flexibility and helix geometry—useful for structure probing, specificity control, and XNA research.

Show Products and Notes
Product/Modification Description/Notes Applications Code
Unlocked Nucleic Acids (UNA) Flexible analog; lowers duplex melting temperature (Tm). Structure probing; specificity tuning; reduce aggregation. Tm ↓ [UNA]
Glycol Nucleic Acid (GNA) Acyclic sugar mimic; high duplex specificity. Synthetic biology (XNA); structural studies; biosensors. Acyclic [GNA]
Threose Nucleic Acid (TNA) Four-carbon threose sugar; unique backbone repeat; nuclease-resistant. Synthetic biology (XNA); enzyme engineering and plymerase testing; stable aptamer and diagnostic probe design Acyclic [TNA]
Hexitol Nucleic Acid (HNA) Non-natural hexitol sugar; nuclease-resistant. Aptamer selection (SELEX); stable probes; diagnostics. XNA [HNA]
Cyclohexene Nucleic Acid (CeNA) Rigid cyclohexene sugar; alters helical geometry. Antisense research; structure–function studies. Rigid [CeNA]
Technical Notes
  • Affinity & Tm: UNA typically lowers Tm (~1–3 °C per residue). GNA/HNA/CeNA/TNA show context-dependent Tm; verify with short test duplexes.
  • Pairing rules: Many XNAs pair best with themselves; cross-pairing with DNA/RNA varies (TNA can cross-pair with altered thermodynamics). Limit consecutive flexible residues.
  • Placement: Keep flexible analogs out of RNase-H gaps; they’re suitable in wings or internal probe positions. For siRNA, avoid the seed if using non-natural XNAs.
  • Backbone: Use PS for in-serum stability. If Tm drops, compensate with length (+1 base) or sprinkle 2′-OMe/MOE or occasional LNA at termini.
  • Synthesis: Some XNA amidites require longer coupling/alternative activators—pilot first. Prefer RP-HPLC; consider PAGE for challenging constructs.
  • QC: Confirm identity by ESI-MS/MALDI with analytical HPLC/CE. Document extinction coefficient differences and report OD/µmol.
  • Serum stability: Run 10–100% serum panels; flexible/acyclic sugars resist nucleases but may alter protein interactions/PK.
  • Modeling: Nearest-neighbor Tm models are less accurate—empirically calibrate in your buffer (Na+/Mg2+, pH).
  • Mix & match: Use UNA to reduce off-targets/aggregation; add sparse LNA/cEt at ends to restore Tm. Keep XNA↔RNA/DNA junctions short.

Speak to Scientist

Design & Strategy

Strategy & Architecture

  • Gapmer ASO: LNA/cEt/MOE wings + DNA core on PS backbone; evaluate 8–10 bp DNA gap for RNase H.
  • Steric-block: Fully 2′-modified (e.g., 2′-OMe/2′-F mix, LNA) on PS or PN for splice modulation.
  • siRNA duplex: 2′-OMe/2′-F patterns to balance RISC loading and off-target; terminal LNA for stabilization.
  • mRNA/sgRNA: 2′-OMe/Ψ/5-MeC patterns can reduce innate sensing; consult app-specific rules.

Design choices affect Tm, protein binding, and toxicity; we provide modeling and Tm prediction support.

Tm & Pairing Behavior

  • LNA/BNA, cEt: large Tm ↑ per residue; shorter, tighter duplexes; watch for off-target binding.
  • 2′-OMe, MOE: moderate Tm ↑; good for wings and siRNA stabilization.
  • 2′-F: Tm ↑ vs RNA; commonly blended with 2′-OMe in siRNA; consider toxicity limits.
  • UNA: Tm ↓; useful as a flexibility “breaker” to reduce aggregation or tune duplex strength.
  • 4′-Thio, FANA: typically Tm ↑ and nuclease resistance ↑; application-dependent.

RNase H requires DNA-like geometry in the gap; avoid over-modifying the core in gapmers.

Chemistry & QC

Chemistry

  • Supports 2′-OMe, 2′-F, MOE, LNA/BNA, cEt, UNA, FANA, 4′-Thio, ara, HNA (on request).
  • Backbones: PS, PO, PN (select contexts), boranophosphate (by request).
  • Conjugations: Cholesterol, GalNAc, PEG, peptides, dyes, chelators, custom linkers.

Purification via HPLC/PAGE as needed; desalting and diafiltration workflows available.

QC & Documentation

  • Identity by ESI-MS (or alternative for highly modified/degenerate sequences).
  • Purity by HPLC; optional SEC for conjugates; moisture/salt/endotoxin on request.
  • COA with yield (OD/µmol), method parameters, and impurity profile.

ISO 9001 / ISO 13485 alignment; GLP/GMP-like practices as scoped.

FAQ

How do I choose between 2′-OMe, 2′-F, MOE, LNA, and cEt?

For gapmer ASO, start with LNA or cEt wings + DNA gap on PS. For siRNA, blend 2′-OMe/2′-F across strands. MOE offers balanced stability and safety in wings. Selection depends on target, length, and toxicity considerations.

Will sugar modifications block RNase H?

Fully modified strands typically do. Gapmer design preserves a DNA-like core to recruit RNase H while using modified wings for stability.

Can I combine sugar mods with conjugates?

Yes. Cholesterol, GalNAc, PEG, peptide, and dye labels are compatible with most sugar patterns. We can advise on placement and purification.

Can’t find the sugar modification you need?

We routinely source or synthesize specialty phosphoramidites and can align to your internal codes or vendor references.

Speak to a Scientist Browse All Modifications

Speak to a Scientist

Tell us about your sugar-modified oligo project

Full Name *
Email *
Company / Institution *
Phone *
Oligo Type
Scale / Quantity
Sequence Length
Sugar Modifications
Backbone
Conjugations
Desired Tm (if applicable)
Purification
QC Requirements
Timeline
Project Summary *

By submitting, you agree to be contacted regarding your request.

Email Instead

Why Choose Bio-Synthesis

Trusted by biotech leaders worldwide for over 40+ years of delivering high quality, fast and scalable synthetic biology solutions.

Greetings Researchers,

Please be advised that any information, guidelines, writeups, and oral/video/graphic content on our website are intended solely as general guidelines.
It is the researcher's sole responsibility to conduct thorough research on the designs of the products intended for their experiments before submitting
their designs to Biosynthesis for review of production feasibility.
Thank you for your understanding.

Quick Links