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Metal Chelators for Oligonucleotide Modification

Custom DNA and RNA oligos carrying DOTA, NOTA, DTPA, DFO, CB-TE2A, DPA, Eu/Tb and specialty chelators for PET/SPECT radiolabeling, MRI contrast, TR-FRET, phosphate-recognition probes and metal-mediated assay development.

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Chelator-Modified Oligos for Metal Labeling and Probe Design

Bio-Synthesis supports custom chelator-modified oligonucleotides for PET/SPECT radiolabeling, MRI contrast research, lanthanide time-resolved fluorescence, metal-mediated capture and phosphate-recognition probe workflows.

Chelators can be installed through NHS ester, isothiocyanate, maleimide, azide/alkyne click or other reactive handles at the 5′ end, 3′ end or selected internal positions. PEG/TEG linkers are often used to reduce steric effects and preserve hybridization.

Common chelator families include DOTA/NOTA/DTPA, CB-TE2A, DFO, DPA, and Eu/Tb lanthanide chelates. The best choice depends on the metal ion or isotope, labeling conditions, complex stability, assay format, oligo placement and downstream purification/QC plan.

Design Logic: Oligo → Chelator → Metal

metal compatibility drives chelator selection
Oligo
Oligonucleotide DNA, RNA, ASO, siRNA, PNA or probe
Chel
Chelator Handle DOTA, NOTA, DTPA, DFO, DPA, Eu/Tb
M+
Metal / Readout PET, SPECT, MRI, TR-FRET, Capture

Animated flow shows how the oligonucleotide, chelator handle and metal readout are selected as one connected design system.

Radiometal Chelators for Oligonucleotide Modification

The core chelator table from the live page is reorganized as a practical selection guide by chelator family, common reactive forms, metals, application and design note.

DOTA, NOTA, DTPA, DFO and Related Chelators

Choose the chelator around the metal isotope, complex stability, labeling temperature, oligo backbone and final application.

Chelator Family Common Forms Typical Metals Applications Design Note
DOTA p-SCN-Bn-DOTA, DOTA-NHS
64Cu68Ga90Y177Lu
PET/SPECT, targeted radiotherapy Macrocycle; strong in vivo retention
NOTA p-SCN-Bn-NOTA
68Ga64Cu
Rapid 68Ga PET labeling, small-ion stability Fast Ga labeling; compact macrocycle
DTPA p-SCN-Bn-DTPA, DTPA anhydride
111InGd3+Ln3+
SPECT, MRI, lanthanide tags Acyclic; easier coupling but lower long-term stability
TETA / TE2A TETA, TE2A
64Cu
PET research and historical Cu chelation Classic copper chelator family
CB-TE2A Cross-bridged cyclam
64Cu
High-inertness copper labeling Very stable copper complexes
DOTMA Tetramethyl-DOTA
64Cu177Lu
Faster labeling, DOTA variant Hydrophobic DOTA analog
HBED HBED-CC and derivatives
Fe3+68Ga
Alternative 68Ga labeling Strong Ga/Fe chelation
TRAP / DATA TRAP, DATA chelators
68Ga
Rapid mild Ga complexation Room-temperature Ga labeling
H4octapa / H6phospa OctaPA, PhosPA
In3+Ln3+
In/Ln labeling with improved kinetics New-generation acyclic chelators
HOPO Hydroxypyridinone derivatives
ActinidesLn3+225Ac
Alpha-therapy research Actinide-focused chelation
DFO Desferrioxamine B, DFO-NHS, DFO-maleimide
89Zr
ImmunoPET and Zr-labeled bioconjugates Gold-standard Zr chelator

Technical notes: Prefer terminal placement when possible to minimize helix perturbation. Use short PEG/TEG linkers to reduce steric effects. For radiometal work, maintain mild metal-compatible buffers and confirm both apo- and metal-loaded states when required.

DPA and Lanthanide Chelators for Sensing and TR-FRET

Smaller chelators are useful for phosphate recognition, optical probes, bacterial membrane targeting and long-lifetime Eu/Tb time-resolved fluorescence labels.

DPA, Zn-DPA, Eu/Tb and Lanthanide Tags

Use compact probe chelators when the goal is sensing, recognition or optical readout rather than long-term in-vivo radiometal retention.

Chelator / Derivative Common Forms Typical Metals Applications Design Note
2′,2′-Dipicolylamine (DPA) Amine, NHS, azide
Zn2+; also Cu2+/Mn2+
Phosphate recognition, bacterial membrane targeting, responsive probes Zn-DPA phosphate-binding
DPA-dye constructs Zn-DPA fluorophore conjugates
Zn2+
Turn-on fluorescence, pathogen detection, membrane imaging Responsive fluorescent probes
DTPA-Eu / DTPA-Tb Lanthanide chelates
Eu3+ / Tb3+
Time-resolved fluorescence and TR-FRET oligo labels Long-lifetime emission
EDTA-Ln derivatives Research-grade EDTA lanthanide tags
Ln3+
Budget TR-FRET and sensing Acyclic lanthanide format
Cyclen / cyclam chromophores Small macrocyclic lanthanide chelates
Eu3+ / Tb3+
Bright lanthanide probes, FRET donors Cyclen-Ln probe family

Probe notes: DPA is compact and useful for phosphate-rich surfaces, but it is not the same as macrocyclic radiometal chelators. Lanthanide tags require compatible buffers and avoidance of competing chelators such as EDTA during assays.

Choose Chelator by Metal and Application

Fast Chelator Selection Guide

Start with the metal or assay readout, then refine by labeling conditions, stability requirement and oligo architecture.

68Ga PET

NOTA, TRAP/DATA, DOTA depending on kinetics and labeling conditions.

177Lu / 90Y

DOTA-based chelators for radiotherapy-oriented workflows.

89Zr ImmunoPET

DFO or DFO derivatives for zirconium-based labeling.

TR-FRET

DTPA-Eu/Tb or cyclen/cyclam lanthanide tags.

Phosphate Recognition

Zn-DPA motifs for phosphate-rich surfaces and responsive probes.

Design and Analytical Confirmation

DES

Conjugation Strategy

  • Select active handle: NHS, p-SCN, maleimide or click
  • Use terminal placement when possible
  • Add PEG/TEG spacers to reduce steric clash
MET

Metal Loading

  • Use mild metal-compatible buffers
  • Validate labeling on a short test sequence when needed
  • Confirm demetallated and metal-loaded forms
QC

QC & Documentation

  • HPLC purity and identity confirmation
  • ESI-MS/MALDI for apo or loaded state
  • Optional ICP-MS, SEC or radiochemical analysis

Applications for Chelator-Modified Oligonucleotides

Chelator-modified oligos are used when nucleic acid recognition must be combined with radiometal labeling, metal-mediated sensing, lanthanide emission or metal-dependent capture.

PET

PET / SPECT Probe Development

Radiometal-labeled oligos for imaging and tracer development studies.

MRI

MRI Contrast Research

Gd/DTPA-style and metal-chelate oligos for contrast and multimodal probe design.

TRF

TR-FRET & Lanthanide Labels

Eu/Tb chelates for long-lifetime fluorescent labels and time-resolved detection.

DPA

Phosphate Recognition Probes

Zn-DPA motifs for phosphate-rich surfaces, membrane targeting and responsive probes.

AOC

Oligo Bioconjugates

Chelator-oligo intermediates for antibody, peptide, protein or nanoparticle conjugates.

CAP

Metal-Mediated Capture

Metal-binding probe designs for capture, purification, assay development and sensing.

FAQ

What is the difference between DOTA, NOTA and DTPA?
DOTA and NOTA are macrocyclic chelators with high complex stability and are commonly selected for PET/SPECT radionuclides. DTPA is acyclic and easier to use but is generally less stable long-term. Choice depends on isotope, labeling conditions and in-vivo stability needs.
What metals are compatible with DPA?
DPA is most often used as a Zn2+-DPA phosphate-recognition motif. It can also bind other metals such as Cu2+ or Mn2+, but it is not usually selected for long-term therapeutic radiometal retention.
When should I use DFO?
DFO is commonly used for 89Zr immunoPET and Zr-labeled bioconjugates. It is useful when the project requires zirconium-based imaging chemistry.
How are chelators attached to oligos?
Chelators are commonly supplied with active handles such as NHS ester, isothiocyanate, maleimide, azide or alkyne. They are typically installed at the 5′ or 3′ terminus with PEG or other linkers to reduce steric effects.
Will a chelator change oligo hybridization?
Terminal chelator modifications usually have limited impact on Tm. Internal chelator insertions can affect duplex stability depending on linker length, placement and sequence context.
Which chelators are best for therapeutic radionuclides?
DOTA is commonly used with 177Lu and 90Y, NOTA with 68Ga and 64Cu, and CB-TE2A with 64Cu. The best choice depends on coordination chemistry, labeling conditions and required stability.
Can I combine a chelator with dyes or other tags?
Yes. Designs can combine chelators with dyes, peptides, lipids or affinity handles using orthogonal chemistries. Spacing should be planned to reduce quenching, steric interference or metal-binding competition.
What QC is provided with chelator-oligo conjugates?
Typical QC includes HPLC purity and ESI-MS or MALDI identity confirmation. Metal incorporation can be evaluated by radioactivity, ICP-MS or other metal-specific assays when requested.
How should chelator-modified oligos be stored?
Lyophilized chelator-modified oligos are typically stored at -20 °C. In solution, use metal-free buffer, aliquot to avoid freeze-thaw cycles and protect from light if dyes are present.

Need help selecting a chelator-metal system?

Share your sequence, oligo type, chelator target, metal or isotope, attachment position, reactive handle, scale, purification target, metal-loading plan and QC requirements. Bio-Synthesis can help align chelator chemistry, linker architecture and analytical confirmation with the intended application.

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