Peptide–Morpholino Conjugation Services
PMO & ThioMorpholino™ (TMO)

Steric-blocking antisense conjugates with defined peptide attachment, purification, and fit‑for‑purpose QC documentation.

High-quality peptide–PMO and peptide–ThioMorpholino™ (TMO) conjugates for steric-blocking antisense delivery

Steric-blocking antisense
PMO & TMO platforms
Site-defined peptide attachment
ISO 9001:2015 / ISO 13485:2016
45+ Years of Expertise
U.S. Facilities - Texas

Overview

Peptide–morpholino conjugates for steric-blocking antisense

Peptide–morpholino conjugates are chemically defined antisense constructs in which a peptide is covalently linked to a morpholino oligomer to support cellular association and delivery while preserving steric-blocking activity.

Bio-Synthesis provides peptide–morpholino conjugation services for programs using charge-neutral steric-blocking antisense agents, supporting both traditional PMO (phosphorodiamidate morpholino oligomers) and ThioMorpholino™ (TMO) platforms. We synthesize and qualify peptide–PMO and peptide–TMO conjugates using site-defined handles, practical conjugation routes (solid-phase or solution-phase), and analytical verification aligned to your program stage, with purification and fit-for-purpose QC documentation. This service complements our broader oligonucleotide conjugation capabilities.

Morpholino antisense agents typically act by blocking RNA interactions (for example, splice-site recognition or ribosome access), rather than recruiting enzymatic RNA-cleavage pathways. Peptide conjugation can support delivery concepts, including targeting ligands and CPP designs, while maintaining a single, chemically defined construct suitable for reproducible characterization and comparative studies.

This service complements our broader oligonucleotide conjugation and antisense modification capabilities.

Steric-blocking antisense
PMO & TMO platforms
Site-defined peptide attachment
Solid- or solution-phase coupling
Purification + QC documentation

Related services: Peptide Modifications, Peptide Bioconjugation, Cell-Penetrating Peptides (CPPs).

Why morpholino?

Mechanism: steric blocking

Morpholino antisense agents are commonly used as steric blockers to modulate splicing or translation by hybridizing to a complementary RNA region and blocking a biological interaction.

  • Splice modulation (exon skipping / inclusion)
  • Translation blocking (start-site or ribosome access interference)
  • High nuclease resistance supports longer exposure in many systems
Why add a peptide?

Peptide conjugation is used to support cellular association and delivery concepts, including receptor-targeting ligands and CPP uptake designs. Conjugates are designed to remain chemically defined for purification and analytical qualification.

  • Targeting ligands (receptor-binding peptides)
  • CPP options (program-dependent; avoid overclaims)
  • Linker/spacer tuning for stability vs release (project-dependent)
CMC-safe mechanism note (no overclaims)

Peptides in morpholino conjugates may support uptake via multiple pathways (e.g., receptor-mediated endocytosis for targeted ligands and other routes for cationic CPP designs). Peptide/linker selection balances solubility, stability, and analytical clarity with the intended delivery concept.

Traditional PMO vs ThioMorpholino™ (TMO)

Platform selection: match chemistry + design space to your target

We support both traditional PMO and TMO constructs. Route selection (solid-phase vs solution-phase) depends on platform, handle placement, and purification/QC strategy.

  • PMO: phosphorodiamidate backbone; charge-neutral steric-blocking antisense
  • TMO: thiophosphoramidate backbone; expanded synthetic flexibility (reported)
  • Both: nuclease-resistant; do not rely on RNase H or RISC mechanisms

Compared to PMO, ThioMorpholino™ (TMO) designs expand chemical flexibility by enabling phosphoramidite-style synthesis and broader modification strategies, as reported in the literature.

Traditional morpholino (PMO)
  • Charge-neutral backbone; steric-blocking antisense modality
  • Commonly used for splice modulation and translation blocking
  • Conjugation typically uses predefined terminal handles and chemoselective coupling
Branched peptide synthesis schematic showing a lysine branching core with two to eight peptide arms (MAP-2, MAP-4, MAP-8) and dendrimer for multivalent epitope presentation.

Figure: PMO vs TMO backbone linkage comparison and chimera concept. (Place your provided image in the same folder and keep the filename.)

ThioMorpholino™ (TMO): advantages reported in the literature
  • Backbone chemistry: thiophosphoramidate internucleotide linkage vs phosphorodiamidate in PMO. [1]
  • Phosphoramidite-style synthesis: reported compatibility with standard solid-phase phosphoramidite chemistry (3′→5′). [1]
  • Broader modification space: reported support for TMO–DNA/RNA chimera designs and incorporation of multiple nucleotide modifications (design-dependent). [1]
  • Chemical stability: reported enhanced chemical stability/resistance in biological settings (model-dependent). [1]
  • Target engagement: reported strong target RNA binding in certain designs (sequence/context-dependent). [1]
  • Specificity by design: expanded design options can support allele-selective strategies (target-dependent). [3]

These points summarize published findings; performance depends on sequence, chemistry map, target accessibility, and biological model.

Published examples (peer-reviewed, reported)
  • Exon skipping (Duchenne muscular dystrophy context): A PNAS study reports that thiomorpholino (TMO) designs achieved exon 23 skipping at lower concentrations compared with PMO and selected nucleotide analogs. [1]
  • Allele-selective knockdown (FUS): A TMO gapmer achieved higher allele-selective knockdown of the FUS gene compared with MOE-modified designs. [2]
  • RNA regulation (TUG1 / intron retention): Thiomorpholino antisense oligonucleotides were used to regulate intron excision and TUG1 RNA. [3]

Reference key: [1] PNAS 2022; [2] Int J Mol Sci 2024; [3] PubMed 2021.

Applications

Splice modulation
  • Exon skipping / exon inclusion workflows
  • Mechanistic splicing studies and controls
  • Sequence- and context-dependent optimization
Translation blocking
  • Start-site blocking and ribosome access interference
  • Research and screening controls
  • Defined conjugates for comparability studies
Targeted delivery concepts
  • Receptor-targeting peptide ligands
  • CPP-based uptake concepts (program-dependent)
  • Endosomal escape motifs (design-dependent)

Conjugation chemistry

Amine/thiol coupling

Chemoselective coupling using defined amine/thiol handles (project-dependent).

  • Defined terminal handles help reduce heterogeneity
  • Spacer selection manages polarity/solubility
  • Reaction monitoring + cleanup aligned to platform
Click-ready handles

Azide/alkyne-type handles for bioorthogonal coupling (program-dependent).

  • High selectivity and robust conversion
  • Useful for orthogonal single-site designs
  • Route chosen to preserve oligo integrity
Stable vs cleavable linkers

Selected based on whether release is required (program-dependent).

  • Stable linkers for permanent attachment
  • Cleavable options when release is needed
  • Spacer length tuned for accessibility
Design inputs (what to send)
  • Platform: PMO or TMO
  • Sequence + target region and intended mechanism (splice/translation)
  • Desired peptide (or “recommend”) + attachment site constraints
  • Linker preference: stable vs cleavable (or “recommend”)
  • Scale, purity, and intended use
Coupling routes: solid-phase vs solution-phase

Peptide–morpholino conjugates can be assembled by solid-phase or solution-phase coupling. Route selection depends on platform, handle placement, and purification strategy.

  • Solid-phase: coupling while one component is on-support (when applicable)
  • Solution-phase: coupling purified components via chemoselective handles
  • Workup: conditions selected to preserve morpholino integrity and conjugate homogeneity

Workflow: from design to delivered conjugate

  • Define construct: platform (PMO/TMO), sequence, modification map, attachment site
  • Build components: peptide synthesis + morpholino preparation with selected handles
  • Conjugate: solid-phase or solution-phase coupling with controlled stoichiometry
  • Purify: RP-HPLC / IEX / SEC as appropriate for construct properties
  • QC & release: identity/purity + documentation aligned to program stage
Development considerations
  • Early feasibility: prioritize defined attachment and clean analytical readouts
  • Later stage: tighten impurity profile and batch-to-batch comparability
  • Plan for solubility/aggregation early (cationic peptides + neutral backbones)

QC and documentation depth can be adjusted to match discovery, preclinical, or later development needs.

Quality control & typical deliverables

Identity & purity
  • Chromatographic purity profile (HPLC/UPLC; IEX/SEC as appropriate)
  • Identity confirmation using suitable orthogonal methods
  • Conjugation confirmation (project-dependent)
Documentation
  • COA aligned to program stage and intended use
  • Synthesis summary and key method notes
  • Batch-to-batch comparability support (as needed)
What you receive
  • Purified peptide–morpholino conjugate
  • QC package and key method details
  • Optional scale-up support (project-dependent)

FAQ

What is a PMO and how does it work?

PMOs are charge-neutral morpholino antisense analogs commonly used as steric blockers to modulate splicing or translation by RNA binding.

What is ThioMorpholino™ (TMO)?

TMO uses a thiophosphoramidate internucleotide linkage. Literature reports compatibility with phosphoramidite-style solid-phase synthesis and broader modification/chimera options (design-dependent).

Do you support CPP–morpholino conjugates?

Yes. We can conjugate CPPs or targeting peptides using site-defined handles and practical coupling routes selected for construct stability and analytical clarity.

What information should I send for a quote?

Platform (PMO/TMO), sequence and target region, desired peptide and attachment constraints, linker preference (stable/cleavable), scale, and purity/usage requirements.

Contact & quote request

For the fastest quote, send platform (PMO/TMO), sequence(s), target region, peptide (or “recommend”), desired attachment site constraints, linker preference (stable vs cleavable), quantity/purity targets, and intended use. We’ll recommend a practical route plus purification/QC aligned to your program stage.

Fastest path
Request a Quote Compare PMO vs TMO

P26-01-30

Fast quote checklist
  • Platform: PMO or TMO
  • Sequence + target region (splice/translation)
  • Peptide choice + attachment site constraints
  • Linker preference (stable/cleavable) or “recommend”
  • Quantity (mg) + purity target + intended use

Recommended reading

Peer-reviewed references supporting ThioMorpholino™ (TMO) chemistry and reported applications.

References provided for scientific context; Bio-Synthesis does not claim ownership of the cited works.

Why Choose Bio-Synthesis

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