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Spacer & Linker Oligonucleotide Modifications

Enhance oligonucleotide performance with custom spacer & linker modifications - Backed by expert design and full QC from research to GMP-like supply.

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Control Distance, Flexibility and Function in Modified Oligos

Spacer and linker modifications are used when the oligo needs controlled distance from a label, surface, conjugation handle, nanoparticle, protein, lipid, dye or affinity tag. The right spacer can reduce steric hindrance, preserve hybridization, improve solubility, support click chemistry or enable controlled release.

Bio-Synthesis supports short alkyl spacers, extended C9-C12 linkers, flexible hydrophilic Sp18/HEG, PEG and azido-PEG spacers, photocleavable PC spacers, and abasic d/rSpacer designs for structural or enzymatic studies. The live-site product table is preserved below under Spacers & Linkers.

C2-C6 Compact spacing for fine geometry control.
Sp18 / HEG Flexible hydrophilic spacing for steric relief.
PC Spacer Light-triggered release or capture control.
Azido PEG Click-ready PEG reach and solubility.
Geometry & Sterics
C2-C6 spacers provide compact separation; C9-C12, Sp18 and PEG provide additional reach for bulky cargo or surfaces.
Hydrophilicity & Solubility
PEG/HEG spacers can improve mobility and reduce aggregation compared with purely alkyl spacer systems.
Orthogonal Workflows
Azido-PEG spacers enable SPAAC or CuAAC click chemistry while also adding flexible distance.

Choose the Spacer by Function, Not Just Length

The spacer should be selected based on the intended role: compact distance control, steric relief, hydrophilic mobility, click-ready conjugation, photocleavable release or non-informational abasic spacing.

C2

Compact Alkyl Spacers

Use C2-C6 when the design needs short, controlled spacing with minimal added bulk.

C2 C3 C4 C5
HEG

Flexible Hydrophilic Reach

Use Sp18/HEG, PEG or longer spacers to reduce steric interference near surfaces, dyes or large payloads.

Sp18 HEG C9 C12
N3

Click-Ready PEG Spacers

Azido PEG3/12/24 spacers combine bioorthogonal azide chemistry with tunable PEG distance.

SPAAC CuAAC Azido PEG
PC

Photocleavable & Abasic Designs

PC spacers support light-triggered release; d/rAbasic sites create programmable non-informational gaps.

PC Spacer dSpacer rSpacer

Spacers & Linkers

Availability by position is indicative. Check marks indicate positions that are commonly supported; ask if a project requires a position not listed.

Spacers & Linkers

Preserved live-site product matrix with cleaner formatting for readability.

Product 5′ Int 3′ Function Application Code
Abasic Site (dSpacer abasic furan-THF) Non-informational gap; enzyme/repair studies Structural mapping; controlled mismatches [dSpacer]
Photocleavable PC Spacer Light-triggered cleavage Photo-controlled capture/release [PC-Spacer]
PC Spacer C3 (photocleavable) Short PC linker with compact spacing Solid-phase or solution cleavage workflows [PC Sp3]
rAbasic Site (rSpacer abasic furan) RNA abasic analog; non-informational gap RNA structure/repair, enzyme probing [rAbasic]
Spacer 18 (hexaethyleneglycol, HEG) Flexible hydrophilic spacing; steric relief Conjugation geometry; hybridization tuning [Sp18]
Spacer 9 Medium alkyl spacer Distance control; reduce quenching [Sp9]
Spacer C12 Longer alkyl spacer; added reach Bulky labels; surface/particle attachment [SpC12]
Spacer C2 Very short alkyl spacer Fine geometry control [SpC2]
Spacer C3 Short alkyl spacer Compact separation for labels [SpC3]
Spacer C4 Short-medium alkyl spacer Distance/sterics tuning [SpC4]
Spacer C6 Medium alkyl spacer; common default Conjugation and surface chemistries [SpC6]
Spacer C9 Medium-long alkyl spacer Reduce sterics; broaden reach [Spc9]
ribo rSpacer RNA-compatible spacer RNA constructs; structural spacing [rSp]
Azido PEG12 Click-ready PEG spacer SPAAC/CuAAC bioorthogonal labeling [Azido PEG12]
Azido PEG24 Longer PEG for added reach/solubility Large payloads; surfaces/NPs [Azido PEG24]
Azido PEG3 Short PEG; compact click handle Minimal perturbation conjugation [Azido PEG3]

Placement

Use 5′/3′ termini for conjugation; internal placements benefit from flexible PEG/HEG to preserve Tm.

Length selection

C2-C6 for compact spacing; C12-Sp18/PEG for bulky labels or surfaces.

Photocleavage

PC spacers enable reversible capture and on-demand release with UV/visible light, depending on assay conditions.

Click chemistry

Azido-PEG spacers support SPAAC/CuAAC; maintain copper-free conditions for sensitive targets.

Tm impact

Flexible hydrophilic spacers such as PEG/HEG generally preserve duplex stability better than short rigid linkers.

QC

Identity by ESI-MS/MALDI and purity by HPLC; optional SEC for high-molecular-weight conjugates.

Where Spacer and Linker Oligos Add Value

GEO

Conjugation Geometry

Control distance between the oligo and dye, peptide, lipid, protein, chelator, surface or nanoparticle.

SUR

Surface & Nanoparticle Assembly

Provide reach and mobility for chips, beads, membranes, gold nanoparticles and biosensor surfaces.

PCR

Probe & Assay Design

Reduce quenching, tune hybridization behavior and support controlled capture/release workflows.

N3

Bioorthogonal Labeling

Use azido-PEG spacers for selective attachment of dyes, peptides, lipids or other click-ready payloads.

PC

Photo-Controlled Release

Use PC spacers when your workflow requires reversible capture, light-triggered cleavage or time-resolved release.

ABA

Abasic Structural Studies

Use dSpacer, rSpacer or rAbasic sites for non-informational gaps, repair studies and enzyme probing.

Purification, QC and Scale Support

PUR

Purification

  • RP-HPLC or IE-HPLC as appropriate
  • PAGE when needed for complex oligos
  • Desalting for selected workflows
  • SEC optional for high-MW conjugates
MS

Analytical QC

  • ESI-MS or MALDI identity confirmation
  • Analytical HPLC purity
  • Optional cleavage verification
  • Application-specific assay support
DOC

Documentation

  • COA and method documentation
  • Research-grade to scale-up support
  • GLP/GMP-aligned workflows as scoped
  • Project-specific QC planning

FAQ

How do I choose between alkyl, HEG/Sp18, and PEG spacers?
Use alkyl spacers for compact inert spacing, HEG/Sp18 for flexible hydrophilic reach, and PEG or azido-PEG when you need both reach and solubility or a click-ready handle.
Do spacers change duplex stability?
Short rigid spacers near hybridization sites may affect Tm. Flexible PEG/HEG spacers generally preserve duplex behavior better, but critical internal placements should be tested.
When should I use a photocleavable spacer?
Use a photocleavable PC spacer when the workflow requires reversible capture, light-triggered release, time-resolved cleavage or controlled surface release.
What QC is provided?
Standard QC can include ESI-MS or MALDI identity confirmation and HPLC purity. SEC, cleavage verification or functional assays can be added for high-MW or application-specific constructs.
Can spacers be placed internally?
 Yes. Many spacers can be incorporated at 5′, internal or 3′ positions, but internal placement should be evaluated against hybridization, steric and functional requirements.
Which spacer should I use for surfaces or bulky payloads?
 For surfaces, nanoparticles or bulky labels, Sp18/HEG, C12 or PEG-based spacers are often better than very short alkyl spacers because they provide reach and flexibility.

Need help choosing the right spacer or linker?

Share your sequence, desired spacer or linker, position, payload or surface, assay goal, scale, purification target and QC needs. Bio-Synthesis can recommend C2-C12, Sp18/HEG, PEG/azido-PEG, PC spacer or abasic designs for your workflow.

Related Product

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Fast Quote Checklist

Include sequence, position, spacer/linker type, application, scale, purification and QC needs.

Sequence Position Spacer Scale QC

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