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Non-Canonical Structure Oligonucleotides

Custom DNA and RNA oligonucleotides engineered to form G-quadruplexes, i-motifs, triplexes, Z-DNA/Z-RNA, hairpins, cruciforms, Hoogsteen-pairing motifs and R-loop scaffolds for structural biology, biosensing, gene regulation and therapeutic research.

G-Quadruplex i-Motif & Triplex Z-DNA / Z-RNA R-Loop Scaffolds Labels, Linkers & Controls
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Overview Selection Guide Structures Design Strategy Analytics Representative Formats Applications Reading FAQ Contact
Overview

Structure-Directed Oligos Beyond the Watson-Crick Helix

Non-canonical nucleic acid architectures extend beyond standard Watson-Crick duplexes to support switchable sensors, gene regulation probes, ligand screening models, structural biology assays and therapeutic motif research. Bio-Synthesis designs and manufactures oligonucleotides intended to fold into defined structures under user-specified buffer, pH, ionic strength and temperature conditions.

These projects require more than ordinary sequence synthesis. G-quadruplex, i-motif, triplex, Z-DNA/Z-RNA, hairpin, cruciform and R-loop systems often depend on sequence context, cation selection, protonation state, topology, label placement and stabilization chemistry.

Bio-Synthesis can integrate stabilizing sugars, backbone edits, terminal caps, fluorophores, quenchers, biotin, PEG spacers, click handles and conjugates while supporting purification, analytical QC and optional structure-focused characterization.

µmol to Multi-GramUPLC / HPLC • LC-MSOptional CD / Melt / Native PAGERUO to GMP-like Pathways
Linear Oligo Sequence, backbone, labels and spacer design.
Controlled Folding pH, cations, temperature and annealing protocol.
Functional Structure G4, i-motif, TFO, Z-form, hairpin or R-loop.
G4
iM
TFO
Z
HP
RLP
Non-Canonical Structure Selection Guide

Non-Canonical Structure Selection Guide

Use this guide to match your research goal to a suitable non-canonical structure, then refine sequence, buffer, labels, stabilization chemistry and analytical confirmation around the chosen model.

Research Goal, Structure Choice & Design Logic

This replaces the clickable product/notes layout with a decision-making map that helps scientists choose a starting structure.

Structure selection guide for non-canonical nucleic acid oligonucleotide design.

Research Goal Best Structure Why It Fits Design Inputs Useful Readouts
pH-switchable sensor i-Motif C-rich structures with intercalated C·C+ pairs respond sharply to mildly acidic pH. pH window, buffer, C-rich sequence, reversibility target. CD, stopped-flow fluorescence, FRET, UV-melt.
Ligand screening / telomere model G-Quadruplex G-tetrads stabilized by K+ or Na+ support ligand binding and topology studies. Cation system, loop length, topology preference, label placement. CD, thermal melt, FRET, native PAGE, ligand-induced stabilization.
Site-specific gene targeting Triplex-Forming Oligo Third-strand Hoogsteen or reverse-Hoogsteen binding targets purine-rich duplex regions. Target duplex tract, pH, Mg2+, interruption tolerance. Gel shift, footprinting, crosslinking, melt analysis.
Innate immune / ZBP1 studies Z-DNA / Z-RNA Left-handed helices favored by alternating purine-pyrimidine repeats and supercoiling. Repeat length, salt/cation system, protein-binding requirements. CD, FRET transition assay, protein binding assay.
Replication / repair models Hairpin / Cruciform Stem-loop and palindromic structures model polymerase stalling, nuclease mapping and repair processes. Stem length, loop composition, GC content, mismatch sites. Native PAGE, nuclease assay, helicase/polymerase readouts.
Transcription collision models R-Loop Scaffold RNA:DNA hybrids with displaced ssDNA model R-loop biology and genome stability. RNA strand design, displaced ssDNA length, stabilization chemistry. Footprinting, protein binding, FRET, nuclease sensitivity.
Structures We Support

Non-Canonical Structures We Support

The live page contains valuable structure categories; this redesign keeps them while removing the expandable catalog feeling and presenting each as a clear scientific capability.

G4

G-Quadruplex Oligonucleotides

G-rich sequences folding into stacked tetrads with topology tuned by sequence, loop design and cation conditions.

Telomere Models Ligand Screening
iM

i-Motif Oligonucleotides

C-rich, pH-responsive structures using intercalated C·C+ pairs for reversible switching and biosensor designs.

pH Sensors Switches
TFO

Triplex-Forming Oligos

Third-strand oligos designed for Hoogsteen or reverse-Hoogsteen pairing with purine-rich duplex targets.

Gene Targeting Footprinting
Z

Z-DNA / Z-RNA Constructs

Left-handed nucleic acid motifs for B-to-Z transition studies, Z-domain recognition and innate immune models.

ZBP1 ADAR1
HP

Hairpin Structures

Defined stem-loop structures for polymerase, nuclease, helicase, mismatch and fluorescence turn-on assays.

Stem-Loop Reporter
CF

Cruciform Structures

Palindromic and inverted-repeat designs for structure extrusion, repair pathway and protein-binding studies.

Palindromes Repair Models
RLP

R-Loop Scaffolds

Pre-assembled RNA:DNA hybrids with displaced ssDNA for transcription-replication conflict and genome stability research.

RNA:DNA Hybrid ssDNA Displacement
CTL

Controls, Ligands & Reporters

Non-folding controls, topology mutants, positive controls, G4 ligand assays and labeled FRET/turn-on probes.

Controls FRET Panels
Design & Stabilization

Design & Stabilization Strategies

Non-canonical structure oligos should be designed around the folding core, non-critical modification sites, assay conditions and required analytical confirmation.

Backbone & Sugar Engineering

LNA, BNA, cEt, 2′-OMe and 2′-F can improve stability when positioned away from critical folding contacts.

  • Loop/stem optimization
  • Improved Tm
  • Nuclease resistance

Structural Stabilization

Terminal caps, partial phosphorothioate placement, PEG spacers and sequence truncation can improve handling and folding behavior.

  • Caps and partial PS
  • PEG / TEG spacers
  • Topology tuning

Labels & Functional Handles

Fluorophores, quenchers, biotin, click handles and affinity tags can be placed at termini or non-critical loops.

  • FAM, Cy5, ATTO, BHQ
  • Biotin / streptavidin
  • Azide, DBCO, TCO

Conjugates & Delivery Tags

GalNAc, peptide, antibody, PEGylation and other conjugation options can be considered when structure and sterics allow.

  • GalNAc and peptides
  • Antibody conjugation
  • Custom bioconjugates
Analytical Characterization

Analytical & Structure-Confirmation Options

Bio-Synthesis supports standard oligo release testing and optional structure-focused readouts when folding behavior needs to be confirmed.

QC

Release QC

UPLC/HPLC purification, LC-MS when applicable, yield documentation and Certificate of Analysis.

CD

CD / UV-Melt

Optional circular dichroism and thermal melt workflows for G4, i-motif, Z-form and other structural motifs.

GEL

Native PAGE / FRET

Native gel snapshots, FRET assays and turn-on reporter formats can help monitor folding, topology or ligand response.

Representative Formats

Representative Non-Canonical Oligo Formats

The live page contains valuable Product & Notes information, but it does not need to appear as a long product drawer. This compact format keeps the key examples, codes and design notes in a shorter decision-friendly layout.

G-Quadruplex (G4) Formats

G-rich oligos and modified guanine analogs for G-tetrad stabilization, topology control, ligand screening and telomere or aptamer model systems.

[G4-8AmG] [G4-7d8aG] [G4-8oxo] [G4-8Br] [G4-7dz]

i-Motif DNA Formats

C-rich pH-responsive constructs using cytosine analogs and epigenetic base variants for reversible folding and sensor workflows.

[iM-2FANA] [iM-5FdCIII] [iM-Ac5MeC] [iM-5FdC] [iM-5hmdCII] [iM-5IdC] [iM-5BrC] [iM-5CarC] [iM-5MeC]

Triplex / TFO Formats

Triplex-forming oligos using Hoogsteen or reverse-Hoogsteen binding with stabilizing base analogs and crosslinking-compatible designs.

[TFO-8AmA] [TFO-8AmG] [TFO-6tG] [TFO-ψU]

Z-DNA / Z-RNA Formats

Alternating purine-pyrimidine scaffolds and labeled reporters for left-handed helix transition, Z-domain recognition and innate immune studies.

[ZDNA-CG] [ZRNA] [Z-FRET]

Hairpin, Cruciform & R-Loop Scaffolds

Defined stem-loop, palindromic and RNA:DNA hybrid models for replication stress, repair, transcription-conflict and structure-processing assays.

[HP-Std] [CF-Pal] [HP-FRET] [RLP-Core] [RLP-FRET] [RLP-Stab]

Reporters, Ligand Assays & Controls

Reporter probes, topology panels, non-folding controls and positive-control sets for structure-activity and specificity studies.

[HG-Dx] [Alt-Pair] [G4-ThT] [G4-Panel] [G4-Comp] [NC-Ctrl] [Topo-Mut] [PCS-Set]

Compact Product & Design Notes Matrix

A shorter consolidated view of the original product-and-notes content from the live page.

Structure Group Representative Products / Modifications Primary Function Key Design Notes
G-Quadruplex 8-Amino-dG, 7-Deaza-8-aza-dG, 8-oxo-dG, 8-Br-dG, 7-deaza-dG Stabilize, destabilize or tune G4 topology and Hoogsteen interactions. Plan K+/Na+ conditions, loop length, topology controls, CD/UV-melt/FRET readouts and non-folding controls.
i-Motif 2′-F-Ac-C-ANA, 5-formyl-dC, Ac-5-Me-dC, 5-hm-dC, 5-I-dC, 5-Br-dC, 5-carboxy-dC, 5-Me-dC Control C·C+ pairing, pH response and reversible folding. Define pH window, buffer strength, temperature, competing G-rich regions and reversibility assay.
Triplex / TFO 8-Amino-dA, 8-Amino-dG, 6-thio-dG, 2′-deoxypseudoU Improve triplex binding, gene-targeting stability and crosslinking or footprinting workflows. Map purine tracts, manage pH/Mg2+ effects and consider psoralen or reporter handles when capture is needed.
Z-DNA / Z-RNA Alternating d(CG)n, Z-RNA motifs, labeled B↔Z reporters Model left-handed helices and B/Z transition behavior. Use alternating repeats, salt or protein conditions, and FRET or CD readouts for transition monitoring.
Hairpin / Cruciform Stem-loop hairpins, palindromic cruciforms, dye-quencher hairpin reporters Model folding, nuclease processing, polymerase stalling and protein recognition. Define stem length, loop sequence, GC content, palindrome design and reporter placement.
R-Loop Scaffolds RNA:DNA hybrids, labeled R-loops, stabilized R-loop constructs Support R-loop binding, resolution, footprinting and transcription-repair models. Use RNA/DNA strand planning, displaced ssDNA design, 2′-OMe/2′-F stabilization and nuclease protection.
Alternative Pairing Hoogsteen-biased duplexes, mismatch probes, altered hydrogen-bonding models Force or detect alternative pairing states and repair/proofreading behavior. Use defined mismatch positions, purine-rich tracts and appropriate structural validation.
Ligand Assays & Controls ThT-compatible G4, topology panel sets, competition assay G4, non-folding controls, topology mutants, positive-control sets Enable ligand screening, selectivity mapping, assay benchmarking and structure validation. Always include matched controls, mutated/disrupted variants and positive controls when screening ligands or reporters.

Ordering note: For quote requests, provide the intended structure, full sequence or target motif, desired modification codes, folding buffer or pH/ion conditions, labels or conjugates, control sequences, purification target and analytical confirmation needs.

Applications

Applications for Non-Canonical Structure Oligos

Structure-informed oligonucleotides support mechanistic research, assay development, ligand screening and model systems that cannot be addressed with ordinary linear duplex oligos.

G4

G4 Ligand Screening

G-quadruplex panels and FRET reporters for small-molecule binding, topology and telomere model studies.

Application Use Case

pH

pH-Responsive Biosensors

i-motif oligos engineered for pH switching, fluorescence response and reversible folding assays.

Application Use Case

TFO

Triplex Gene Targeting

Triplex-forming oligos for promoter targeting, footprinting, mutagenesis and sequence-specific duplex recognition.

Application Use Case

DDR

DNA Repair & Replication Models

Hairpin, cruciform and alternative-pairing motifs for polymerase, nuclease, repair and replication stress studies.

Application Use Case

RLP

R-Loop Biology

RNA:DNA hybrid scaffolds with displaced ssDNA for transcription-replication conflict and genome stability research.

Application Use Case

IMM

Innate Immune Recognition

Z-DNA/Z-RNA and structure-biased motifs for Z-domain recognition and immune signaling model studies.

Application Use Case

SAR

Structure-Activity Studies

Mutant panels, modified-base series and topology controls to compare folding, stability and activity.

Application Use Case

FRET

FRET Structural Probes

Labeled oligos for folding kinetics, ligand response, turn-on assays and conformational monitoring.

Application Use Case

FAQ

How do I specify buffers for proper folding?
Provide target K+, Na+ or Mg2+ concentration, pH, temperature and pre-folding steps such as heat-cool or annealing. These parameters are especially important for G4, i-motif, triplex and Z-form designs.
Which stabilizing chemistries are compatible?
Common options include LNA/BNA blocks, cEt, 2′-OMe, 2′-F, terminal caps and partial phosphorothioate placement. Modifications are typically positioned away from the folding core unless they are part of the structure design.
Can labels and linkers be added without disrupting the structure?
Yes. Dyes, quenchers, biotin, PEG and click handles such as azide, DBCO or TCO can often be placed on termini or non-critical loop regions with flexible TEG or PEG spacers.
Do you provide structure confirmation data?
Standard QC includes UPLC or HPLC and LC-MS when applicable. Optional CD spectra, UV-melt, native PAGE snapshots and FRET-style assays can be added for structure-focused programs.
What information helps start a non-canonical structure project?
Provide motif type, sequence or target region, desired structure, pH and buffer conditions, cation requirements, labels/linkers, scale, purification target and required analytical QC.
Can Bio-Synthesis make control oligos?
 Yes. Non-folding controls, base-shuffled variants, topology-switch mutants and positive control sets can be designed to support assay qualification and specificity testing.
More FAQ'sAll FAQ's
Contact & Quote Request

Need help designing a non-canonical oligo structure?

Share your target structure, sequence constraints, buffer conditions, pH and ion requirements, labels, stabilization chemistry, scale and analytical needs. Bio-Synthesis can help design and manufacture structure-informed oligonucleotides with appropriate purification and QC.
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Email: info@biosyn.com
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Fast Quote Checklist

Include motif, sequence, buffer, pH, cations, labels, scale and QC.

Motif Buffer pH Labels QC
Scientific Background & Recommended Reading

Recommended Reading & Literature References

Selected references are provided for general scientific context around non-canonical nucleic acid structures, folding biology and structural readouts. They are not product-performance claims.

  1. Rhodes D, Lipps HJ. G-quadruplexes and their regulatory roles in biology. Nucleic Acids Research. 2015;43(18):8627-8637. DOI
  2. Gehring K, Leroy JL, Gueron M. A tetrameric DNA structure with protonated cytosine-cytosine base pairs. Nature. 1993;363:561-565. DOI
  3. Frank-Kamenetskii MD, Mirkin SM. Triplex DNA structures. Annual Review of Biochemistry. 1995;64:65-95. DOI
  4. Herbert A. Z-DNA and Z-RNA in human disease. Communications Biology. 2019;2:7. DOI
  5. Santos-Pereira JM, Aguilera A. R loops: new modulators of genome dynamics and function. Nature Reviews Genetics. 2015;16:583-597. DOI

Note: Final sequence design should account for target motif, buffer, ionic conditions, pH, temperature, label placement, folding protocol and the analytical method used to verify structure.

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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.

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