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In-Sequence Chemistry

Internal Oligo Modifications

Reactive handles (amino, thiol, azide/alkyne, aldehyde), internal fluorescent bases & quenchers, spacers/linkers, photocrosslinkers, and stability analogs. “Product & notes” panels include nested Technical Notes. First category opens by default.

Overview Reactive Handles Fluorescent & Quenchers Spacers & Linkers Photocrosslinkers Stability & Sugar Analogs

Overview — Internal DNA/RNA Oligo Modifications

Internal oligo modifications add chemistry within the DNA/RNA sequence to enable bioconjugation (internal amino, thiol, azide/alkyne, aldehyde), built-in reporters (internal fluorescent bases & quenchers), geometry control (HEG/TEG & alkyl spacers), photocrosslinking (psoralen, halogenated, thio bases such as 5-iodo-dT), and stability tuning (LNA, 2′-OMe, 2′-F, UNA/TNA). Common use cases: custom qPCR/FRET probes, protein–nucleic-acid crosslinking, and ASO/siRNA optimization.

Bio-Synthesis provides design consulting (probe architecture, FRET spacing, gapmer/siRNA rules), scalable synthesis (nmol → gram), and ISO-aligned QC (HPLC, ESI-MS; optional CE/SEC and functional tests). Explore related pages: Spacer & Linker Modifications and Quencher Compatibility.

Probe Design Click-Ready Photocrosslink Tm & Stability ISO 9001/13485

Internal Reactive Handles (Amino, Thiol, Azide, Alkyne, Aldehyde)

In-sequence NH2, SH, azide/alkyne, aldehyde, halo, SPAAC (DBCO), and lipid/serinol handles for post-synthetic ligation of dyes, peptides, haptens, polymers, chelators.

Hide products and Notes
Product Description Typical Use Code
3′-Azido-Modifier Serinol Internal azide (serinol) handle CuAAC/SPAAC click with DBCO/alkynes [INT-N3-Serinol]
Biotin-TEG Azide Biotin tag with TEG-azide SPAAC to DBCO; capture/immobilization [Bio-TEG-N3]
Desthiobiotin-TEG Azide Reversible biotin analog (N3) Affinity capture with mild elution [dBio-TEG-N3]
Psoralen Azide Psoralen headgroup with azide Click then UV crosslink mapping [Psor-N3]
Coumarin Azide Blue-UV fluorophore (N3) Clickable fluorescent labeling [Coum-N3]
6-FAM-TEG Azide FAM dye with TEG-N3 CuAAC/SPAAC dye attachment [FAM-TEG-N3]
6-HEX Azide HEX dye as azide Clickable probe labeling [HEX-N3]
6-TET Azide TET/JOE family dye (N3) Clickable probe labeling [TET-N3]
Disulfo-Cyanine 7 Azide NIR dye, water-soluble azide Low-background far-red labeling [sCy7-N3]
TEMPO Azide Nitroxide spin-label (N3) EPR/paramagnetic probes [TEMPO-N3]
TEMPO-TEG Azide TEMPO + flexible TEG-N3 Spin label with reduced sterics [TEMPO-TEG-N3]
Dipivaloyl 6-FAM-TEG Azide Masked/lipophilic FAM (N3) Click-labeling with tuned polarity [dp-FAM-TEG-N3]
5′-DBCO-TEG 5′ cyclooctyne with TEG spacer Copper-free SPAAC to azides [5′-DBCO-TEG]
DBCO-dT Internal DBCO on thymidine SPAAC to azides (dyes/ligands) [INT-DBCO-dT]
DBCO-sulfo-NHS Ester Amine-reactive DBCO Install SPAAC handle on NH2-oligos [DBCO-sNHS]
C8-TMS-Alkyne-dC Protected C8-alkyne on dC Deprotect → CuAAC click [C8-TMS-C≡C-dC]
C8-Alkyne-dC Internal C8 terminal alkyne CuAAC click ligation [C8-C≡C-dC]
C8-Alkyne-dT Internal C8 terminal alkyne CuAAC click ligation [C8-C≡C-dT]
3′-Propargyl-5-Me-dC 3′ alkyne on 5-Me-dC 3′ end click labeling [3′-Prg-5Me-dC]
5-Ethynyl-dU 5-ethynyl uridine analog Internal alkyne for click [5-Ethynyl-dU]
Aziobutyrate NHS Ester NHS-activated azido linker Convert NH2-oligo to azide [NHS-Azido-Cn]
5′-Aldehyde-Modifier C2 5′ carbonyl (CHO) handle Oxime/hydrazone ligation [5′-CHO-C2]
5-Formylindole Indole base with aldehyde Carbonyl ligation on base [5-Formyl-Ind]
5′-Bromohexyl 5′ halo-alkyl chain SN2/thiol capture; surfaces [5′-Br-Hexyl]
Amino-Modifier C6 dR Long-arm internal amine NHS-ester coupling (dyes/peptides) [INT-NH2-C6]
Palmitate Serinol C16 lipid on serinol Uptake enhancement; anchoring [Palm-Ser]
Technical Notes
  • SPAAC (DBCO↔Azide) is copper-free. For CuAAC, add TBTA/THPTA and fully remove copper (HPLC/cleanup).
  • Use HEG/TEG spacers near bulky cargos to preserve hybridization and reduce quenching.

Internal Fluorescent & Quencher Bases (FAM, HEX, Cy3/Cy5, BHQ, BBQ)

Internal dyes and dark quenchers for qPCR, molecular beacons, FRET, and imaging.

Hide products and Notes
Product Description Typical Use Code
6-FAM-TEG Azide FAM dye with TEG-azide Clickable dye install for qPCR/FRET [FAM-TEG-N3]
6-HEX Azide HEX dye as azide Clickable labeling (green/yellow) [HEX-N3]
6-TET Azide TET/JOE-like dye as azide Clickable labeling (green-yellow) [TET-N3]
Coumarin Azide Blue-UV fluor via click Environment-sensitive readouts [Coum-N3]
Cyanine 3 Cy3 fluor (orange) qPCR/FRET probes [Cy3]
Cyanine 3.5 Red-shifted Cy3 Wider pairing sets [Cy3.5]
Cyanine 5 Far-red Cy5 Low-background channels [Cy5]
Cyanine 5.5 NIR Cy5.5 NIR detection [Cy5.5]
JOE-dT Internal JOE on dT Beacon/probe reporter [JOE-dT]
Quasar® 570-dT Quasar 570 internal dye Orange-red probe channels [Q570-dT]
Quasar® 670-dT Quasar 670 internal dye Far-red probe channels [Q670-dT]
Thiazole Orange NHS Ester Env-sensitive dye (NHS) Label NH2-oligos for intercalative readouts [TO-NHS]
BHQ™-1 Non-emissive quencher (480–580 nm) FAM/HEX/TET probe quenching [BHQ-1]
BHQ™-2 Non-emissive quencher (560–670 nm) Cy3/ROX probe quenching [BHQ-2]
BBQ-650®-dT Internal dark quencher (red/far-red) Cy5/Quasar 670 beacons/probes [BBQ-650-dT]
Technical Notes
  • Start with 15–25 nt donor↔quencher spacing and add a HEG/TEG spacer near dyes.
  • Prefer dark quenchers (BHQ/BBQ) for multiplex to minimize bleed-through.

Internal Spacers & Linkers (dSpacer, HEG/TEG, 1-Ethynyl)

Abasic sites, alkyl/PEG linkers, and photocleavable linkers for geometry, reach, and steric control.

Hide products and Notes
Product Description Typical Use Code
1-Ethynyl dSpacer Abasic spacer with terminal alkyne Internal click site with minimal base perturbation [dSpacer-C≡CH]
Technical Notes
  • Use longer PEG/HEG or C9–C12 spacers for bulky cargos/surfaces.

Internal Photocrosslinkers (Psoralen, Halogenated, Thio)

UV-activated bases to covalently trap DNA/RNA or NA-protein contacts.

Hide products and Notes
Product Description Typical Use Code
Psoralen C2 Short-reach psoralen crosslinker DNA interstrand crosslinks (320–365 nm) [Psor-C2]
Psoralen C6 Psoralen with longer spacer Crosslinking opposite strand/base [Psor-C6]
Psoralen Azide Clickable psoralen headgroup Site-specific installation then UV crosslink [Psor-N3]
5-I-dT Halogenated thymidine (iodo) UV crosslinking & heavy-atom derivatization [5-I-dT]
TIPS-5-Ethynyl-dU Protected alkyne dU (TIPS) Click handle / photo-probe workflows [TIPS-Eth-dU]
Technical Notes
  • Optimize irradiation dose and oxygen to balance crosslink yield vs damage.

Internal Stability & Sugar Analogs (LNA, 2′-OMe, UNA/TNA)

Locked/bridged bases and 2′-modified sugars to enhance nuclease resistance, affinity, and safety.

Hide products and Notes
Product Description Typical Use Code
2′-OMe-N6-Me-A 2′-O-methyl sugar with N6-methyl adenine Epitranscript mimic; stability/tuning [2′OMe-m6A]
Technical Notes
  • For gapmer ASOs, keep locked bases in wings; maintain a DNA-like RNase-H core.

FAQ

What are internal oligo modifications?

They add functional chemistry within the sequence—amino, thiol, azide/alkyne, aldehyde handles; fluorescent bases and quenchers; spacers/linkers; and photocrosslinkers—for conjugation, reporting, and stability tuning.

How are amino/thiol/azide modifications used in DNA probes?

Amino couples to NHS esters; thiol binds maleimides/gold; azide/alkyne support SPAAC/CuAAC click. Add spacers to reduce sterics.

Which internal fluorescent bases are best for qPCR and FRET?

FAM/BHQ-1 and Cy3/BHQ-2 are common; Cy5/BBQ-650 for far-red. Keep 15–25 nt spacing and add HEG/TEG spacers.

What are photocrosslinking oligonucleotides (psoralen, halogenated)?

Psoralen, 5-iodo-dT, and thio bases form covalent adducts upon UV to trap NA–NA or NA–protein contacts. Useful in structural biology.

Can internal modifications improve siRNA and ASO stability?

Yes. LNA/BNA/cEt, 2′-OMe, and 2′-F raise Tm and resist nucleases. For gapmers, keep DNA-like core for RNase H, modified wings at ends.

What QC is provided for custom internal oligonucleotides?

Standard QC: HPLC purity, ESI-MS identity. Optional CE/SEC and functional tests. ISO-aligned documentation; SKU mapping available.

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