Multivalency & Amplification

Dendrimer & Brancher Modifications

Enhance your oligo functionality with dendrimer and branched modifications for advanced conjugation, multivalent binding, and improved bioavailability.

Overview

Bio-Synthesis provides comprehensive expertise in dendrimer and branched oligonucleotide modifications, enabling the presentation of multiple functional groups, ligands, or payloads from a single oligo backbone. These structures expand oligo functionality by introducing multivalency, signal amplification, and high payload density for advanced research, diagnostics, and therapeutic applications.

Branchers such as Doublers, Treblers, and 5-Me-dC branch sites introduce 2–3 arms for simple multivalent constructs. Dendrimers and dendrons (e.g., PAMAM, Bis-MPA) provide controlled, higher-order valency (G1–G4+) to maximize payload attachment or probe density. These modifications can be combined with PEG/TEG spacers to manage steric effects, improve solubility, and maintain hybridization performance.

We support projects from early discovery through regulated production, offering custom design consultation, scalable synthesis, and full analytical validation (HPLC, SEC, ESI-MS, MALDI, loading analysis). Whether your application requires signal-amplified probes, multivalent aptamers, multifunctional ADC-like conjugates, or high-density surface immobilization, our team delivers tailored solutions aligned with your research and therapeutic goals.

Multivalency Signal Amplification High Payload Density Nanostructures Surface Presentation GLP / GMP Alignment

Dendrimer & Brancher Product Examples

Representative options; additional branch chemistries and custom dendrons are available upon request.

Hide Table and Notes

common end blockers are listed below

Product Description Applications Notes / Code
5-Me-dC Brancher Modified cytosine with internal branch site Internal branching for multi-label or handles [5Me-dC-Branch]
Dendrimer Branch Doubler C2 Bifunctional branching unit (short C2 spacer) Two-arm branched oligos; compact spacing [Doubler-C2]
Dendrimer Branch Doubler C8 Bifunctional branching unit (flexible C8 spacer) Two-arm constructs for bulkier payloads [Doubler-C8]
Dendrimer Branch Trebler Trifunctional branch phosphoramidite Multivalent labeling or payload attachment [Trebler]
Dendrimer Branch Trebler Long Extended trifunctional brancher Added reach to mitigate steric clash [Trebler-Long]
diB-TEG (Doubler TEG) Bifunctional triethylene glycol brancher Hydrophilic spacing; improved solubility [diB-TEG]
PAMAM Dendrimer Poly(amidoamine) dendritic scaffold (valency G1–G4+) High-valency conjugation; delivery & targeting [PAMAM]
Bis-MPA Dendrons Biodegradable dendritic framework Controlled valency with biocompatibility [Bis-MPA]
Branched Linkers PEG/alkyl multi-arm linkers Flexible spacing for bulky conjugates [Branch-Link]
Multivalent Ligand Designed for multiple binding moieties Boost binding avidity or multi-targeting [Multi-Lig]
Hide Technical Notes
Design Tips
  • Start simple: Evaluate Doubler/Trebler at a terminus; add internal branching after Tm verification.
  • Balance hydrophilicity: Prefer TEG/PEG branches for hydrophobic payloads.
  • Avoid critical motifs: Keep branch points out of seed regions (siRNA) and RNase-H cores (gapmers).
  • Valency vs length: More arms may require longer linkers to avoid self-quenching/aggregation.
  • Spacer choice: Use TEG/PEG branches (C6–PEG12) to offset steric bulk and preserve hybridization Tm.
  • Placement: Start at termini; for internal branchers (e.g., 5-Me-dC), avoid seed regions in siRNA and core DNA gaps in RNase-H designs.
  • Valency: Trebler (3-arm) and dendrons (G1–G4+) scale signal/payload but may raise viscosity and retention; plan purification.
  • Purification/QC: HPLC plus SEC or diafiltration recommended for dendrimer conjugates; MS may show broadened envelopes—report average loading.
  • Applications: Aptamer multimerization, probe signal amplification, nanoparticle assembly, high-density surface immobilization.
Key Modification Strategies
  • Dendrimer Conjugation (e.g., PAMAM dendrimer, bis-MPA dendrons)
  • Branched Linkers at the 5′, 3′, or internal positions
  • Multivalent Ligand Display (e.g., GalNAc, peptides, dyes)
  • Spacer-enhanced branching (e.g., PEG-based, alkyl, or nucleotide spacers)

Two main strategies exist for synthesizing oligonucleotide dendrimers. In the divergent approach, the structure grows outward from the core to the periphery. In the convergent approach, growth proceeds inward, from the periphery toward the center. The number of branches added at each step dictates how many cycles are required and ultimately controls both the size of the dendrimer and the density of groups displayed on its surface. The chemical nature of these terminal groups defines the overall properties of the molecule.

Our dendrimeric modifiers allow dendrimer structures to be built either on top of a conventional monomeric oligonucleotide or directly on the solid support at the 3′ end. Furthermore, monomeric and dendrimeric sequence segments can be synthesized in different lengths and orientations by applying either 3′ or 5′ oligonucleotide synthesis chemistries.

Symmetric Doubler 2DNA

The symmetric doubler produces branches with the same oligo sequence.

Symmetric Trebler 3DNA

The symmetric doubler produces branches with the same oligo sequence

Different generations of dendrimeric oligonucleotides

Speak to Scientist

Custom Branching Options

Site-specific incorporation into DNA, RNA, and LNA oligos with compatibility across:

  • Amine- or thiol-modified oligos (NHS / maleimide workflows)
  • Click-ready azide/alkyne handles for orthogonal assembly
  • Dendrimer-oligo conjugates with varying generation sizes
  • PEG spacers (C6–PEG12) to reduce steric hindrance
  • DMT-protected internal branching (e.g., 5-Me-dC branchers)
  • PAMAM / Bis-MPA dendrons for controlled valency
  • PEGylated, GalNAc-modified, and dye-labeled dendritic structures

Delivery Format

  • Purification: HPLC (RP/IEX) and/or SEC for high purity; removes truncates, free dyes, and excess dendrons.
  • QC: Verified by ESI-MS and MALDI-TOF; UV-Vis for dye/ligand loading; optional SEC or CE for complex constructs.
  • Formats: Shipped lyophilized in tubes or 96-well plates; buffer exchange and counter-ion options available.
  • Scale: From 50–100 nmol research lots up to multi-mg or gram-scale; RUO, GLP, or cGMP documentation on request.
  • Packaging: Standard tubes, barcoded vials, or plates; custom labeling and OEM/private-label supply supported.

Design & QC

Design Tips

  • Start simple: Evaluate Doubler/Trebler at a terminus; add internal branching after Tm verification.
  • Balance hydrophilicity: Prefer TEG/PEG branches for hydrophobic payloads.
  • Avoid critical motifs: Keep branch points out of seed regions (siRNA) and RNase-H cores (gapmers).
  • Valency vs length: More arms may require longer linkers to avoid self-quenching/aggregation.

QC & Documentation

  • Identity by ESI-MS/MALDI (expect broader envelopes with dendrimers).
  • Purity by HPLC; consider SEC or diafiltration for high-MW conjugates.
  • Report average loading (dyes/ligands per strand) and counter-ions.
  • CoA with yield (OD/µmol), purity %, branching chemistry, and handles.

Dendrimer & Brancher — Technology & Benefits

How it Works

Branchers (Doubler/Trebler, 5-Me-dC sites) and dendritic scaffolds (PAMAM, Bis-MPA) create multi-arm nodes on a single oligonucleotide. This enables multivalent presentation of labels, ligands, or payloads while preserving hybridization through appropriate spacer lengths (C6–C12, PEG4–PEG12) and orthogonal handles (amine, thiol, azide, alkyne).

Design Principles

  • Placement: Start at 5′/3′ termini for minimal Tm impact; add internal branches (e.g., 5-Me-dC) after pilot Tm tests.
  • Valency control: 2-arm (Doubler), 3-arm (Trebler), or dendrons (G1–G4+) matched to label/payload count.
  • Spacing & sterics: Use C6–C12 or PEG4–PEG12 to avoid self-quenching and maintain duplex stability.
  • Orthogonal assembly: Combine NHS–amine, maleimide–thiol, and CuAAC/SPAAC for clean multi-label builds.
  • QC & cleanup: HPLC for purity; add SEC/diafiltration for higher-MW dendrimers; verify average loading by MS.

Benefits at a Glance

  • Signal amplification: Multiple dyes/redox tags per strand for higher sensitivity.
  • Avidity & targeting: Multivalent ligands/aptamers increase apparent affinity.
  • High payload density: Greater drug/peptide load per oligo.
  • Modular builds: Orthogonal handles simplify multi-step conjugations.
  • Tunable geometry: Valency + spacer length set reach, sterics, and surface density.

Unsure where to branch? We can prototype Doubler vs Trebler with PEG spacing and report Tm, purity, and loading.

Use Case & Why It Helps Typical Setup
Probe signal amplification: Multiple reporters per strand increase sensitivity. Trebler (3-arm) at 3′; PEG4–PEG12 spacers; RP-HPLC; MS loading
Multivalent aptamer binding: Simultaneous interactions raise apparent affinity (avidity). Doubler/Trebler at 5′; dual/tri aptamers; optional surface immobilization
Drug/ligand delivery: Higher payload per oligo strand with controlled valency. Bis-MPA dendron (G1–G3) via NHS/maleimide; HPLC + SEC cleanup
Dense surface presentation: Improved packing on electrodes/microarrays for stronger signals. Thiol–gold immobilization; terminal branch node; optional Fc/MB readouts
Combinatorial multifunction: Mix dyes, ligands, chelators on one scaffold. Orthogonal handles on Trebler; staged conjugation; PEG spacers

FAQ

What’s the difference between a brancher and a dendrimer/dendron?

Branchers (Doubler/Trebler/5-Me-dC) make 2–3 arms directly on the oligo. Dendrimers/dendrons (PAMAM, Bis-MPA) are tree-like scaffolds with higher, controlled valency (G1–G4+). Use branchers for compact multivalency, dendrons for higher payload density.

Will branching affect Tm or hybridization?

Terminal branchers have minimal Tm impact. Internal branching can lower Tm depending on position and spacer length. Start at the 5′/3′ end; use PEG (PEG4–PEG12) or C6–C12 spacers to reduce sterics and self-quenching, then confirm with a short pilot duplex.

Where should I place the branch point?

Prefer termini. If internal, avoid siRNA seed regions and RNase-H cores in gapmers. For aptamers, place the node away from the binding motif and add PEG spacing.

How many labels/payloads can I attach?

Doubler = 2 arms; Trebler = 3. Dendrons scale by generation (e.g., G1 ≈ 3–4, G2 ≈ 6–8, design-dependent). Practical limits are set by sterics, solubility, and application Tm.

What purification and QC do you use?

HPLC (RP/IEX) and/or SEC for high purity. QC includes ESI-MS/MALDI-TOF; UV-Vis for dye/ligand loading; optional analytical SEC or CE for complex dendrimer conjugates. CoA reports yield, purity, and loading..

Can I combine branching with other conjugates (e.g., dyes, redox tags, GalNAc, chelators)?

Yes. We routinely build multi-functional constructs using orthogonal handles (NHS/amine, maleimide/thiol, CuAAC/SPAAC). We’ll stage the order of reactions and use spacers to keep performance intact..

What scales and delivery formats are available?

From 50–100 nmol development lots to multi-mg/gram scale. Shipped lyophilized (tubes or 96-well plates). Buffer exchange and counter-ions on request. RUO, GLP, or cGMP documentation available..

How should I store branched/dendrimer oligos?

Store lyophilized at 4 °C (short-term) or −20 °C (long-term). In solution, use appropriate buffer, aliquot, and minimize freeze–thaw cycles. Protect light-sensitive labels..

What information helps you quote quickly?

Sequence and length, target application, brancher/dendron type (Doubler/Trebler/PAMAM/Bis-MPA), desired valency, placement (5′/internal/3′), linker length (e.g., PEG4–PEG12), payloads (dyes/ligands), scale, and QC/purification needs..

Can you support OEM/private-label or recurring supply?

Yes—barcoded packaging, OEM labels, and long-term supply programs are supported. Tell us your QA/QC and documentation requirements.

Speak to a Scientist

Tell us about your branching/dendrimer project

Please avoid confidential details; we can arrange an NDA if needed.

You’ll receive a confirmation by email.

Why Choose Bio-Synthesis

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