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Conjugation-Ready Oligos

Reactive Oligonucleotide Handlers

Pre-activated oligos for fast, selective bioconjugation — azide/alkyne (CuAAC), DBCO/BCN (SPAAC), TCO/tetrazine (IEDDA), thiol–maleimide, NHS-ester/amine, and aldehyde–oxime/hydrazone workflows.

Overview

Bio‑Synthesis manufactures custom reactive DNA/RNA oligonucleotides pre‑activated for rapid, selective bioconjugation—including azide/alkyne (CuAAC), DBCO/BCN/DIBAC (SPAAC), TCO/tetrazine (IEDDA), thiol–maleimide, NHS‑ester/amine, and aldehyde–oxime/hydrazide workflows. These click‑ready oligos simplify building probes, conjugates, and surfaces/nanoparticles for diagnostics, research, and therapeutic development.

Place handles at the 5′, 3′, or internal position, with spacer engineering (e.g., TEG/PEG) to reduce sterics and improve yield. We support nmol → multi‑gram scales with HPLC/PAGE purification, identity confirmation by ESI‑MS, optional endotoxin/residual solvent testing, and documentation for ISO 9001/13485 programs (RUO through ISO‑aligned production). Need help picking the optimal chemistry or orthogonal pair? Our scientists will optimize design and QC for your application.

Azide / Alkyne DBCO / SPAAC TCO / Tetrazine Thiol–Maleimide NHS / Amine Aldehyde–Oxime ISO 13485
Services at a glance
  • Custom pre‑activated oligos (5′/3′/internal) with TEG/PEG spacer options.
  • Conjugation design: orthogonal handle sets, spacer length, stoichiometry & buffers.
  • Analytical QC: HPLC/PAGE, ESI‑MS; optional endotoxin/residual solvent.
  • Scale‑up & documentation: RUO to ISO 9001/13485 support with lot files & COAs.
  • Related: enzyme‑oligo conjugates, biotinylated capture oligos, diagnostic oligos.

SEO Keywords: reactive oligonucleotide handlers, click‑chemistry oligos, azide oligo, DBCO oligo, TCO tetrazine oligo, maleimide oligo, NHS‑ester oligo, custom DNA/RNA conjugation, ISO 13485 oligo manufacturing.

Azide / Alkyne (CuAAC)

Copper‑catalyzed azide–alkyne cycloaddition (CuAAC) installs stable triazoles for robust bioconjugation. Use when copper is acceptable and precise control of reaction timing is desired; pair azides with terminal alkynes or propargylated sites on proteins, peptides, or surfaces.

Hide Products & Notes
Products 5-Prime Internal 3-Prime Linker Type Common Uses Code
Azido-Alkyne Spacer Y Y Azide and terminal alkyne Sequential click labeling (CuAAC + SPAAC) [5Alk]
Azide–PEG–NHS Y Y Azide + NHS ester Amine conjugation + click-ready for azide–alkyne reactions [5N3]
Biotin-Azide Y Y Biotin tag + azide group Click-based streptavidin targeting [5N3]
Alkyne-Azide-FAM Y Y Triple: FAM + azide + alkyne Multimodal imaging or capture [5N3]
Alkyne–PEG–NHS Y Y Alkyne + NHS ester CuAAC click handle + NHS coupling to proteins/oligos [5Alk]
Azido–PEG4–Alkyne Y Y Click linker with azide and terminal alkyne Dual labeling, targeted delivery systems [5Alk]
Mal–PEG–Azide Y Y Maleimide + Azide Dual bioconjugation: thiol attachment + SPAAC [5N3]
Mal–PEG–Alkyne Y Y Maleimide + Alkyne Dual conjugation: thiol + CuAAC click [5Alk]
FAM–PEG–Azide Y Y Fluorescent dye + azide Imaging oligo conjugates [5N3]
Azide–PEG–OH Y Y Azide only Click handle to react with alkyne or DBCO partners [5N3]
Click-Ready Dual Handle [RXH]
5'Azide NHS Y –N? Surface coupling, fluorophore/PEG/drug attachment [5N3]
3'-Azide Y –N? Surface coupling, fluorophore/PEG/drug attachment [3N3]
5'-Alkyne Y –C?CH Click to azide-tagged molecules [5Alk]
Mal-amido-PEG-alkyne Y Maleimide + Alkyne + PEG Azide-modified dyes, peptides, biotin [5Alk]
5'-Azide-PEGn Y –N? with spacer Flexible linker for biomolecule or nanoparticle joining [5N3]
Alkyne-dU Y Alkyne-modified base Internal clickable alkyne handle [iAlk]
Click-Ready Dual Handle Y Y Azide + TCO Two-step orthogonal click for complex bioassembly [5RXH]
Technical Notes
  • Catalyst: Cu(I) + stabilizing ligands (TBTA/THPTA) improve biocompatibility.
  • Sequence placement: Avoid copper near sensitive thiols; click first, then thiol chemistry.

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Copper‑Free Click (DBCO/BCN/DIBAC)

Strain‑promoted azide–alkyne cycloaddition (SPAAC) with DBCO/BCN/DIBAC avoids copper, enabling conjugation directly on proteins, cells, and live systems. Great for low‑toxic contexts and hard‑to‑dialysis partners; add PEG spacers to reduce steric hindrance.

Show Products & Notes
Products 5-Prime Internal 3-Prime Linker Type Common Uses Code
DBCO-Biotin Y Y DBCO + Biotin Copper-free click to azide + purification [5DBCO]
DBCO–PEG4–NHS Y Y Strained alkyne (DBCO) and NHS ester Copper-free click for protein–oligo systems [5DBCO]
Mal–PEG–DBCO Y Y Maleimide + DBCO Thiol-based linkage + copper-free click [5DBCO]
DBCO–PEG–OH Y Y DBCO only Copper-free click labeling, PEGylated intermediate [5DBCO]
5'DBCO / DBCO-dT Y Strained Alkyne Copper-free labeling of azide probes [5DBCO]
5'-BCN Y Cyclooctyne Alternative to DBCO, less bulky [5BCN]
TCO-PEG(n)-DBCO Y Y Y [5DBCO]
DBCO-PEGn Y Strained alkyne + PEG Improved solubility, low steric hindrance for azide labeling [5DBCO]
BCN-PEG(n) Y Cyclooctyne + PEG Flexible linker for azide conjugation [5BCN]
Technical Notes
  • Kinetics: SPAAC is slower than IEDDA but metal‑free; ideal for proteins/cells.
  • Hydrophilicity: PEGylated cyclooctynes often improve yields in crowded matrices.

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IEDDA Click (TCO/Tetrazine)

Inverse‑electron‑demand Diels–Alder (IEDDA) between TCO and tetrazine offers ultrafast kinetics and high specificity—ideal at low concentrations or for sequential, orthogonal builds. Protect TCO from light/oxygen and use fresh solutions for best performance.

Show Products & Notes
Products 5-Prime Internal 3-Prime Linker Type Common Uses Code
TCO–PEG–Biotin Y Y TCO + biotin on flexible PEG Tetrazine ligation + affinity purification [5TCO]
TCO–PEG–OH Y Y TCO only Fast click to tetrazine, bioorthogonal ligation [5TCO]
Tetrazine-dT Y Y Y Tetrazine Super-fast ligation with trans-cyclooctene (TCO) [5TZ]
5'-TCO C6 Amidite Y Trans-Cyclooctene Clicks with Tetrazine [5TCO]
TCO-PEG(n)-NHS Y Y Y Trans-Cyclooctene Clicks with Tetrazine [5TCO]
Tz-TCO Conjugate Y Tetrazine + TCO Rapid bio-orthogonal delivery or photolabile systems [iTCO]
Technical Notes
  • Speed: Among the fastest bio‑orthogonal reactions; excellent at low abundance.
  • Orthogonal sets: Combine with SPAAC or maleimide for multi‑site builds.

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Thiol‑Reactive (Maleimide/Haloacetyl/Disulfide)

Handles for sulfhydryl chemistry (maleimide, haloacetyl, pyridyl‑disulfide) enable selective labeling of Cys residues or reduced disulfides. Optimize pH (≈6.5–7.5 for maleimide) and consider releasable disulfides for triggerable payloads.

Show Products & Notes
Products 5-Prime Internal 3-Prime Linker Type Common Uses Code
Thiol Modifier [RXH]
5'-Thiol C6 Y 6-carbon alkyl thiol (-SH) Protein conjugation, maleimide labeling, gold surface attachment [5RXH]
Thiol C6 S-S Y Y Y 6-carbon disulfide (-S–S–) Thiol introduction via disulfide; reduced prior to use [5RXH]
Dithiol Serinol Y Y Y 2× thiol on serinol backbone Multivalent gold/metal surface binding, crosslinking [5RXH]
Thiol C6-dT Y Y Y Thiol on dT base with 6-carbon linker Site-specific internal labeling or conjugation [5RXH]
3'-Dithiol Serinol Y Serinol with 2× thiol 3?-anchored bidentate thiol linker [3RXH]
3'-Thiol C3 S-S Y 3-carbon disulfide Compact 3? disulfide linker for release or capture [3RXH]
3'-Thiol 6 S-S Y 6-carbon disulfide Common for 3? thiol-based surface conjugation [3RXH]
Maleimide / Maleimide-NHS [Mal]
5'-Maleimide C6 Y 6-carbon maleimide linker Conjugation to thiol-modified biomolecules (proteins, peptides, thiolated oligos) [5Mal]
5'-Maleimide NHS Ester Y Activated ester of maleimide Dual functionality: reacts with amines (NHS) or thiols (maleimide) [5Mal]
3'-Maleimide Y Maleimide linker 3? thiol-targeted conjugation (site-specific) [3Mal]
Maleimide-dT (internal) Y Y Y Maleimide on thymidine Internal conjugation to thiol-bearing compounds or surfaces [5Mal]
Maleimide-PEG(n) Linker Y Maleimide with PEG spacer Improved solubility and steric spacing for protein–oligo conjugates [5Mal]
Amino-Thiol C6 Linker Y Y Alkyl or PEG with both –NH? and –SH Dual labeling: amide + maleimide conjugation [5AmC6]
Maleimide-NHS Y Y Maleimide with NHS-ester Thiol-to-amine bridge (e.g., protein to oligo) [5Mal]
Thiol-PEG-Amine Y Y Thiol and amine on PEG linker Spacer for dual conjugation and stealth effect [5AmPEG]
NHS–PEG–Maleimide Y Y PEG linker with NHS ester + maleimide Oligo–protein or oligo–peptide conjugation (site-specific) [5Mal]
Technical Notes
  • pH control: Maleimide reacts best at pH ~6.5–7.5; limit competing amines.
  • Cleavable options: Use pyridyl‑disulfide for reversible linkages.

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Primary Amine (–NH₂) Handlers

Primary‑amine modifiers add or expose –NH₂ groups for downstream NHS/TFP/ITC coupling or electrostatic attachment. Choose spacer length (C6/TEG/PEGn) to balance reach vs. compactness; control hydrolysis for active esters during subsequent coupling.

Show Products & Notes
Products 5-Prime Internal 3-Prime Linker Type Common Uses Code
5'-Amino Modifier 5 Y 5-carbon atoms (short) Surface attachment, solid-phase labeling [5AmC5]
5'-Amino C6 Y 6-carbon atoms (flexible) Fluorophore or quencher conjugation, NHS-ester labeling [5AmC6]
5'-Amino C12 Y 12-carbon spacer Longer spacer for reduced crowding, hydrophobic linkers [5AmC12]
5'-Amino TEG Y TEG (triethylene glycol) Improved solubility and spacer for aqueous bioconjugation [5AmTEG]
5'-Amino Modifier 11 Y 11-carbon linear chain Used in surface coupling, longer spacing from oligo [5AmC11]
5'-Amino C3 Y 3-carbon chain Minimal spacer, limited flexibility [5AmC3]
PC Amino Modifier Y Y Y 6-carbon spacer UV-cleavable linker, which leave 5'-phosphate upon photolysis [5AmC6]
Amino Modifier C6 Y Y Y 6-carbon chain Versatile – for 5', 3', and internal labeling [5AmC6]
Amino-C2 dT Y Y Y 2-carbon chain Internal labeling at thymidine base [5AmC2]
Amino-C6 dT Y Y Y 6-carbon chain Used for internal probe labeling (dT) [5AmC6]
Amino-C6 dA Y Y Y 6-carbon chain Internal labeling on adenine (dA) base [5AmC6]
N2-Amino-C6 dG Y Y Y 6-carbon chain at guanine N2 Labeling at guanine base (N2 position) [5AmC6]
Amino Serinol Y Y Y Serinol backbone (2C + OH) Used for RNA/DNA linker arms, good solubility [5Am]
Amino C6 rU Y Y Y 6-carbon linker on uridine Internal RNA labeling [5AmC6]
3'-Amino C6 Y 6-carbon chain 3? terminal labeling and bioconjugation [3AmC6]
3'-Amino C6 dT Y 6-carbon at thymidine 3? modified thymidine for labels [3AmC6]
3'-Amino C3 Y 3-carbon Compact 3? modification [3AmC3]
3'-Amino C7 Y 7-carbon Extended 3? linker for better reach [3AmC7]
3'-Amino Serinol Y Serinol linker Water-soluble 3? modifier [3Am]
Technical Notes
  • Active esters: NHS/TFP/ITC are moisture‑sensitive—prepare fresh and couple promptly.
  • Stoichiometry: Excess amine partners can drive completion; quench unused esters.

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Aldehyde / Oxime / Hydrazide

Carbonyl chemistry (oxime/hydrazone) enables chemoselective ligation to aldehyde‑bearing partners. Use anilinium catalysts for near‑neutral buffers; post‑coupling reduction can stabilize linkages when required.

Show Products & Notes
Products 5-Prime Internal 3-Prime Linker Type Common Uses Code
Aldehyde Modifier [Ald]
5'-Aldehyde C2 Y Terminal aldehyde (-CHO) Conjugation via oxime or hydrazone ligation to hydrazides or aminooxy groups [5Ald]
Aldehyde-dT (internal) Y Y Y Aldehyde on modified thymidine Used for internal coupling to hydrazide-functionalized probes [5Ald]
3'-Aldehyde Y Terminal aldehyde End-labeling for conjugation to hydrazide- or aminooxy-modified surfaces [3Ald]
Aldehyde-PEG Y Aldehyde with PEG spacer Bioconjugation where longer linker and solubility are needed [5Ald]
5-Formylindoe Y Y Y Formyl on indole ring Internal or terminal labeling for conjugation via aldehyde-reactive chemistry [5RXH]
Technical Notes
  • Acceleration: Anilinium catalysis boosts rates in near‑neutral buffers.
  • Stabilization: Reductive amination can lock linkages after screening.

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Carboxyl (EDC/NHS)

Carboxyl activation via EDC with NHS/TFP generates amine‑reactive esters for rapid coupling. Prepare fresh and couple promptly; remove urea byproducts and excess reagents via desalting or SEC.

Show Products & Notes
Products 5-Prime Internal 3-Prime Linker Type Common Uses Code
Carboxy / NHS-Carboxy [NHS]
5-Carboxy Modifier C10 Y 10-carbon carboxy linker Covalent coupling to amines via EDC/NHS chemistry, surface immobilization [5COOH]
5'-NHS-Carboxy Y NHS-activated ester (short linker) Direct reaction with primary amines, useful for protein/peptide labeling [5NHS]
3'-Carboxy Modifier Y Short or medium chain carboxyl Allows coupling to surfaces (e.g., beads, slides) or bifunctional linkers [3COOH]
3'-NHS-Carboxy Y NHS ester Instant amine conjugation at 3? terminus [3NHS]
Carboxy-dT Y Y Y Carboxyl on modified base Internal labeling with NHS-reactive group for crosslinking or spacer attachment [5COOH]
Technical Notes
  • Activation time: Couple immediately after EDC/NHS formation to reduce hydrolysis.
  • Cleanup: Desalting/SEC removes urea byproducts and boosts purity.

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Other / Specialty

Specialty or less common handles (e.g., vinylsulfone, iodoacetyl, multi‑functional adapters) cover unique assay geometries and orthogonality requirements. Contact us to plan spacing, sequence placement, and purification for complex builds.

Show Products & Notes
Products 5-Prime Internal 3-Prime Linker Type Common Uses Code
Products Linker Type Common Uses [RXH]
Products Linker Type Common Uses [RXH]
Products Linker Type Common Uses [RXH]
Products Linker Type Common Uses [RXH]
Glyceryl Modifier [RXH]
Products Linker Type Common Uses [RXH]
5'-Glyceryl Modifier Y Vicinal diol group (-CH(OH)-CH2OH) Surface attachment via periodate oxidation (to aldehydes), useful for slide or bead immobilization [5RXH]
3'-Glyceryl Modifier Y Vicinal diol on 3? terminus Capture onto aldehyde-activated surfaces (e.g., aldehyde-coated glass) [3RXH]
Glyceryl-dT Y Y Y Modified thymidine with vicinal diol Internal anchoring or capture via oxidation and reductive amination [5RXH]
Bifunctional Modifier [RXH]
Products Linker Type Common Uses [RXH]
Mal-PEG(n)-PFP Y Y Maleimide + Pentafluorophenyl ester Amine–thiol bridging; PEGylation; hydrolytically stable alternative to NHS [5RXH]
Mal-PEG(n)-t-butyl ester Y Y Maleimide + t-butyl ester Thiol conjugation with latent carboxyl handle (t-butyl removable) [5RXH]
Mal-amido-PEG(n)-acid Y Y Maleimide + PEG-carboxylic acid Bioconjugation to thiols; carboxy terminus for EDC/NHS coupling [5RXH]
Mal-amido-PEG-acid Y Y Maleimide + PEG-acid (short) Shorter PEG spacer variant; EDC/NHS coupling to amines [5RXH]
Biotin–PEG–NHS Y Y Affinity tag + NHS ester Capture and labeling of amine-functionalized oligos or peptides [5NHS]
Mono-Functional PEG Linker [RXH]
Products Linker Type Common Uses [RXH]
NHS–PEG (up to PEG40) Y Y NHS ester only For amine-targeted PEGylation (oligo, protein, peptide) [5NHS]
mPEG(n)–NHS Y Y Methoxy + NHS PEGylation of primary amines with non-reactive end (methoxy cap) [5NHS]
m-PEG(n)-Mal Y Y Methoxy + Maleimide PEGylation of thiol-containing targets; non-reactive methoxy terminus [5RXH]
Mal–PEG–OH Y Y Maleimide only Conjugation to thiols; free hydroxyl terminus [5RXH]
Products Linker Type Common Uses [RXH]
Dual Modifiers Y Azide + Alkyne Enable multistep or orthogonal labeling [5RXH]
Azido-dU Y Azide-modified base Internal azide for precise labeling or pull-down [iRXH]
Technical Notes
  • Compatibility: Verify orthogonality with other handles and assay buffers.

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FAQ

What QC is recommended?

HPLC and MS identity are standard. For conjugates, consider SEC/desalting and functional assays.

Do I need a spacer?

TEG/PEG spacers often improve reach and reduce sterics, increasing coupling efficiency and function.

How do I choose the right handler?

Match handler to partner chemistry (thiol, amine, azide/tetrazine). Consider orthogonality if using multiple handles.

Need help selecting the optimal reactive handler?

We’ll match the chemistry to your payload, optimize spacer length, and define purification & QC for your scale.

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