Lipopeptide Synthesis

Custom lipidated peptides and lipid–peptide conjugates with site-defined attachment—designed for reproducibility, assay-ready performance, and scalable delivery.

ISO 900:2015/ISO13485:2016 45+ Years of Expertise U.S. Facilities - Texas Custom Lipopeptides N-Terminal, C-Terminal & Side-Chain Lipidation Fit-for-purpose QC (HPLC/MS)

Overview

Site-defined lipidation for membrane affinity, self-assembly, and immunology workflows

Bio-Synthesis provides custom lipopeptide synthesis and lipid–peptide conjugation services for projects where lipidation changes function—improving membrane association, enabling amphiphilic self-assembly, enhancing delivery, or introducing immune-active lipid motifs.

We support N-terminal acylation (N-lipidation), side-chain lipidation (e.g., Lys ε-amine), and site-selective conjugation (e.g., Cys handles). Each project is planned using sequence-aware SPPS (and fragment strategies when needed) with protecting-group orthogonality to control selectivity and reduce product heterogeneity.

Deliverables are aligned to your decision needs, with a fit-for-purpose purification and QC strategy (HPLC/MS standard; expanded testing available) to ensure the final material is usable in formulation, binding, immunology, or mechanistic studies.

N-terminal (N-acyl) lipidation Site-defined Lys/Cys lipidation Click-ready handles (azide/alkyne) Hydrophobic-sequence planning Fit-for-purpose QC (HPLC/MS)
Example lipopeptide structures illustrating N-terminal and side-chain lipidation
Figure: Representative lipopeptide architectures showing N-terminal acylation and site-defined side-chain lipidation.
Site-specific

A defined attachment site reduces mixtures and improves batch-to-batch reproducibility.

Sequence-aware

Hydrophobicity and aggregation risks are planned up front to protect yield and purity.

Fit-for-purpose QC

HPLC/MS standard; optional analytics selected based on formulation and downstream requirements.

Related services: Peptide Modifications, Vaccine Peptides, Peptide Conjugates. For ready-made options, browse Catalog Peptides.

What is a lipopeptide?

Working definition

A lipopeptide is a peptide bearing a covalently attached lipid (fatty acid, sterol, or amphiphile). The lipid can increase membrane affinity, drive supramolecular assembly, and tune distribution or immune engagement depending on the architecture.

  • Defined lipid identity and attachment site(s)
  • Controlled linkage/chemistry (project-dependent)
  • Common in delivery, vaccine, and membrane-targeting studies
Why site-definition matters

Lipidation can easily create mixtures if multiple reactive sites exist (e.g., multiple Lys residues). Site-defined designs improve interpretability and reproducibility across assays and batches.

  • Cleaner structure–function relationships
  • More consistent chromatography and formulation behavior
  • Better comparability across analog series (lipid or site variants)

Lipidation types we synthesize

N-terminal lipidation (N-acyl)

A direct and common architecture. Typically yields one dominant product when the N-terminus is uniquely available.

  • Fatty acid acylation (C12–C18 and beyond)
  • Linker insertion (optional) to tune spacing
  • Useful for membrane association and self-assembly studies
Side-chain lipidation (site-defined)

Lipid attached to a defined residue (commonly Lys ε-amine) to preserve N-terminus or control presentation.

  • Orthogonal protection strategy for selectivity
  • Reduces heterogeneity in multi-Lys sequences
  • Flexible placement to protect binding motifs
C-terminal lipidation (C-terminal conjugation)

Attach the lipid to the peptide C-terminus (e.g., via C-terminal carboxylate or a defined C-terminal handle) to preserve N-terminal motifs or control orientation.

  • C-terminal acylation/conjugation routes (project-dependent)
  • Useful when N-terminus must remain free for binding/processing
  • Can reduce competing N-terminal modifications in multi-step designs
Lipidation placement: side-chain vs handle-based

A compact schematic comparing site-defined side-chain lipidation with handle-based late-stage conjugation for modular lipid screening.

Side-chain lipidation (site-defined) Defined Lys (or other) site using orthogonal protection Handle-based conjugation (Cys / click) Azide/Alkyne Modular lipid swapping without resynthesizing peptide core
Figure: Two common routes to site-controlled lipidation — side-chain lipidation vs handle-based conjugation.
Handle-based conjugation (Cys / click)

Late-stage modular lipidation using a defined handle—ideal for screening lipid variants on one peptide core.

  • Cys-selective conjugation options (project-dependent)
  • Azide/alkyne handles for modular chemistry
  • Efficient analog series generation
Common project formats
  • Lipidated antigen constructs (self-adjuvanting designs)
  • Membrane-anchored probes and receptor ligands
  • Amphiphilic assemblies (micelles, nanofibers)
  • Lipid or linker scanning panels (SAR exploration)
  • Conjugation-ready peptides (handles on request)
  • Matched controls (non-lipidated peptide core)

Typical lipids we incorporate

Practical lipid menu (examples)

Below is a practical list of commonly requested lipid moieties. Availability and the best route depend on the lipid structure, desired attachment chemistry, sequence behavior, and whether you need a single defined product.

  • Saturated fatty acids: lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18)
  • Shorter/longer chains: capryloyl (C8), caproyl (C6), arachidoyl (C20) (project-dependent)
  • Branched/unsaturated: oleoyl (C18:1) and analogs (project-dependent)
  • Lipid spacers: β-Ala, aminohexanoic acid (Ahx), PEG spacers (when needed)
  • Sterols: cholesterol and sterol-linker conjugates
  • Immunology motifs: di-/tri-palmitoylated cysteine-based motifs (project-dependent)
  • Amphiphiles: PEG-lipids and lipid-like amphiphiles (project-dependent)
  • Custom lipids: customer-supplied lipids or target analogs (reviewed for compatibility)

Not sure what lipid to choose? Tell us your target (membrane anchoring, self-assembly, immune activation, or PK tuning) and the assay/formulation constraints. We’ll recommend a practical design and QC plan aligned to your decision.

Synthesis workflow

1) Design review

Confirm sequence, lipid target, attachment site(s), and any required handles (azide/alkyne, cysteine, biotin, etc.).

  • Risk check: hydrophobicity & aggregation
  • Site-definition plan (orthogonal protection)
  • Purity/quantity targets aligned to use
2) Synthesis strategy

SPPS of peptide core + on-resin or solution lipidation; fragment strategies available for challenging designs.

  • Coupling and deprotection optimization
  • Linker/handle implementation (if needed)
  • Cleavage/workup tuned for hydrophobic products
3) Purification & QC

Deliver assay-ready material with identity/purity documentation and optional characterization as needed.

  • MS identity confirmation
  • Analytical HPLC profile
  • Optional testing (endotoxin, residual solvents, etc.)
What to send for a fast quote
  • Peptide sequence(s) and length
  • Target lipid (or functional goal if undecided)
  • Attachment site preference (N-terminus / Lys / Cys / handle)
  • Quantity and purity target
  • Downstream use (vaccine, membrane assay, self-assembly, etc.)
  • Any required labels/handles and documentation needs

Comparison table

Buyers searching “lipopeptide synthesis” typically compare vendors on site definition, control of mixtures, technical transparency, and QC clarity. Use this checklist to evaluate any provider.

Approach Site-defined Mixture control Technical transparency QC clarity Best fit
Design-led SPPS + defined lipidation step High HPLC/MS + options Most custom N-terminal and site-defined side-chain lipopeptides
SPPS + handle-based modular conjugation High Project-specific Analog series and lipid-screening on a common peptide core
“Standard” catalog-style offerings Low Varies Quick procurement when an exact match exists
Mixture-prone workflows (poorly specified) × × Low Minimal Not recommended when reproducibility matters

If you want ready-made peptides (non-lipidated), see Catalog Peptides. For defined lipidation, request a custom quote.

Applications

Vaccines & immunology
  • Self-adjuvanting lipidated constructs
  • Antigen delivery and presentation studies
  • Defined analog series for SAR
Membrane & receptor studies
  • Membrane-anchored probes
  • Receptor binding and trafficking assays
  • Localized presentation of ligands
Self-assembly & materials
  • Amphiphilic assemblies (micelles/nanofibers)
  • Biophysical characterization inputs
  • Formulation and dispersion studies
Common reasons lipopeptides fail (and how we plan around it)
  • Aggregation on-resin: coupling strategy and backbone mobility planning
  • Low solubility: linker/spacer selection; handling and purification strategy
  • Multiple lipidation sites: orthogonal protection or defined handles
  • Purification complexity: method selection adapted to hydrophobic analytes
  • Adsorption losses: workup and container selection considerations
  • Analytical ambiguity: QC chosen to match your decision requirements

Quality control & characterization

Standard QC
  • MS identity confirmation
  • Analytical HPLC profile / purity
  • COA + supporting documentation
Optional characterization
  • Additional LC methods (project-dependent)
  • HRMS or expanded identity support (project-dependent)
  • Custom documentation bundles
When to add more

If your goal is to compare lipid variants, prove site definition, or support regulated workflows, tell us what the data must demonstrate—then we’ll recommend the right options.

  • Compare lipid/linker analog series
  • Validate site-defined attachment
  • Support publication- or GMP-aligned reporting

Specifications & typical deliverables

Use this as a checklist for your quote request. If you’re unsure, send your sequence(s) and goal—we’ll propose options.

Parameter Typical options Notes for lipopeptide projects
Attachment type N-terminal (N-acyl), side-chain (Lys/Cys), handle-based (azide/alkyne) Specify site(s) if a single defined product is required; we’ll plan orthogonality.
Lipid identity Fatty acids (C12–C18 and beyond), sterols, amphiphiles (project-dependent) Provide lipid name/structure if available; customer-supplied lipids can be reviewed.
Sequence behavior Project-dependent Hydrophobic sequences may benefit from design adjustments, linkers, or fragment routes.
Quantity µg–mg+ (project-dependent) Hydrophobicity and purification strategy affect recovery; expectations set early.
Purity Crude to higher purity upon request Purity targets should match downstream use; method tuning may be needed.
Standard deliverables COA, MS, HPLC Optional testing available (endotoxin, residual solvents, peptide content, etc.).

FAQ

Can you make both N-terminal and side-chain lipidated peptides?

Yes. We support N-terminal acylation, C-terminal lipidation (project-dependent), and site-defined side-chain lipidation (commonly Lys). We also support handle-based strategies for Cys-selective or modular lipidation when appropriate.

What do you need from me to start a lipopeptide project?

Send your peptide sequence(s), lipid identity (or goal if undecided), desired attachment site(s), target quantity/purity, and downstream use. If you need a single defined product, tell us whether multiple Lys/Cys are present.

How do you avoid mixtures when multiple sites are reactive?

We plan protecting-group orthogonality and choose a single defined attachment site (or a dedicated handle) to reduce heterogeneous products and improve reproducibility.

What QC is included by default?

Standard deliverables typically include MS identity confirmation, an HPLC profile, and a COA. Optional testing (endotoxin, residual solvents, peptide content, expanded documentation) can be added on request.

Can you supply the non-lipidated peptide as a control?

Often yes. If you need matched controls (peptide core vs lipidated version), include that in your quote request so we can align synthesis and QC.

Why are lipopeptides sometimes difficult to synthesize or purify?

Lipidation increases hydrophobicity and can increase aggregation, reduce solubility, and broaden chromatographic peaks. A design-led plan (site definition, linkers/handles, and tailored purification) reduces risk.

Contact & quote request

Fast quote checklist
  • Sequence(s) + desired attachment site(s)
  • Target lipid (or functional goal)
  • Quantity, purity, and timeline
  • Downstream use and any required labels/handles
Talk to a scientist

Share your sequence and goal—we’ll recommend a practical lipidation strategy and QC plan aligned to your application.

For fastest turnaround, include whether multiple Lys/Cys sites exist and whether a single defined product is required.

Why Choose Bio-Synthesis

Trusted by biotech leaders worldwide for over 40+ years of delivering high quality, fast and scalable synthetic biology solutions.