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N-Terminal Peptide Modification

Site-defined N-terminal chemistry for precise peptide modification and conjugation.

Request a Quote N-terminal library Applications
Over 500+ site-defined N-terminal modifications Click handles (azide/alkyne/DBCO/BCN) Biotin & fluorescent dyes N-terminal conjugation (PEG, lipid, biomolecules)
Overview Advantages Library Applications Workflow QC FAQ Contact

Overview

What is N-terminal peptide modification?

N-terminal peptide modification means installing a defined chemical feature at the peptide’s N-terminus (α-amino group). Because each peptide has exactly one N-terminus, this strategy is inherently site-defined—often delivering a homogeneous product with a predictable mass shift and cleaner analytical interpretation than multi-site side-chain labeling.

Bio-Synthesis supports over 500 peptide modifications, including N-terminal caps (e.g., Ac-, pGlu-), N-terminal labels/handles (biotin, dyes, chelators), click-ready chemistries (azide, alkyne, DBCO, BCN), and PTM-style N-terminus changes (e.g., dimethylation, trimethylation) as well as lipid tails (e.g., palmitoylation, myristoylation) and ubiquitylation / ubiquitin-mimic conjugation (project-dependent), and N-terminal conjugation to functional payloads (PEG, lipids, biomolecules) for orientation-controlled presentation in assays, imaging, and delivery designs.

Our N-terminal peptide modification services cover design consultation, synthesis, purification, and QC for research, diagnostic, and preclinical applications.

N-terminal biotinylated peptide N-terminal click chemistry peptide N-terminal labeling & conjugation N-terminal acetylation peptide N-terminal PTM mimic

The N-terminus marks the start of the peptide chain and contains the free α-amino group (–NH₂). N-terminal modifications selectively target this position to introduce caps, PTM mimics, lipid tails, or conjugation handles while maintaining site-defined control.

Peptide N-terminus structure with acetylation, myristoylation, and palmitoylation examples

Figure: Structural location of the peptide N-terminus (α-amino group) and representative N-terminal modifications such as acetylation and lipidation (myristoylation, palmitoylation).

Related services:
   Peptide Modifications Stapled Peptide Synthesis Cysteine-Specific Chemistry Click Chemistry Peptides Difficult Peptide Synthesis Catalog Peptides
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Advantages of N-terminal modification

Single attachment site

One N-terminus per peptide → positional certainty and reduced product multiplicity vs Lys labeling.

  • Cleaner purification profile
  • Simpler structure assignment
  • More reproducible lots
Stability & protease resistance

N-terminal capping (e.g., acetylation, pGlu) can reduce susceptibility to aminopeptidases and improve functional stability.

  • Improved stability (sequence-dependent)
  • More native-like termini for many peptides
  • Reduced N-terminus charge when needed
Orientation-controlled conjugation

Attach payloads at a defined end to control presentation—critical for imaging, capture reagents, and delivery constructs.

  • Consistent binding/display
  • Controlled stoichiometry
  • Better assay reproducibility
Better analytical performance

Site-defined N-terminus modifications typically yield cleaner LC profiles and predictable intact mass shifts—useful for method development and QC.

  • Cleaner LC-MS interpretation
  • Reduced heterogeneous labeling artifacts
  • Predictable modification mass additions
When NOT to use N-terminal modification

If the free N-terminus is required for activity (e.g., receptor engagement), consider C-terminal or side-chain strategies instead.

  • N-terminus is part of a binding epitope
  • Native processing requires free NH2
  • A unique Cys (or engineered handle) is the best site

N-terminal peptide modification library (representative)

Expand categories to see representative N-terminal peptide modifications with names, functions, and common abbreviations. Need a specific handle not listed? Send the requested structure or catalog number—our team will recommend a practical route.

N-terminal capping (stability & charge control) Ac-, pGlu-, formyl, etc.
N-terminal acetylation pyroglutamate (pGlu) terminal capping
Name of modification Abbrev. Primary function / why it’s used
N-terminal acetylation Ac- Neutralizes N-terminus charge; commonly improves stability vs aminopeptidases and can increase native-like behavior.
N-terminal pyroglutamate (from Gln/Glu) pGlu- / Pyr- Blocks N-terminus; often used to mimic endogenous processing and improve stability in biological matrices.
N-terminal formylation For- Adds a small cap; used to modulate N-terminus reactivity/charge and for specific mechanistic models.
N-terminal succinylation Suc- Introduces negative charge; useful for tuning solubility, charge-driven binding, or separation behavior.

Best pick (most common): Ac- when you want a simple, broadly compatible stability/charge adjustment.

N-terminal labeling (detection & capture) biotin, fluorescent dyes, chelators
N-terminal biotinylation fluorescent labeling imaging & detection
Name of modification Abbrev. Primary function / why it’s used
Biotin Biotin- Affinity capture via avidin/streptavidin; ideal for pull-downs, immobilization, and binding assays with defined orientation.
Fluorescein FAM- / FITC- Fluorescence detection; commonly used for binding assays, microscopy, and flow-based readouts.
Tetramethylrhodamine TAMRA- Red-shifted fluor; useful for multiplexing and lower background than green channel in many assays.
Cy dyes (project-dependent) Cy3-/Cy5-/Cy7- Bright fluorophores for imaging/assays; selection depends on instrument filters and desired photostability.
Metal chelators (project-dependent) DOTA-/NOTA- Chelation of metals for imaging/binding studies; useful for radiometal workflows (project-dependent).

Best pick (capture): N-terminal biotin for high-affinity capture with site-defined stoichiometry.

N-terminal click-ready handles (modular assembly) azide, alkyne, DBCO, BCN
azide alkyne DBCO BCN SPAAC / CuAAC
Handle Abbrev. Primary function / why it’s used
N-terminal azide N3- Bioorthogonal handle for CuAAC or SPAAC (with DBCO/BCN counterpart); enables selective late-stage conjugation.
N-terminal alkyne Alkyne- Partner for CuAAC; widely used for modular assembly and probe attachment.
DBCO (copper-free click partner) DBCO- SPAAC without copper; preferred for sensitive biomolecules/cell workflows.
BCN (copper-free click partner) BCN- SPAAC partner with strong practical reactivity; common in bioconjugation projects.

Best pick (bioorthogonal, copper-free): DBCO/BCN when you want robust click conjugation without copper exposure.

N-terminal PTM mimics (methylation & ubiquitin) dimethyl / trimethyl • Ub
N-terminal methylation dimethylation trimethylation ubiquitylation

These modifications are commonly discussed as post-translational modification (PTM) motifs. When installed at the peptide N-terminus, they are N-terminal peptide modifications and can be used to mimic biology, tune charge, or build defined peptide–protein conjugates.

Name of modification Abbrev. Primary function / why it’s used
N-terminal dimethylation Me2- PTM mimic that can change N-terminus charge/interaction profile; used in mechanistic studies and binding workflows.
N-terminal trimethylation Me3- PTM mimic; can alter recognition and physicochemical behavior. Useful for structure–function comparisons vs unmodified termini.
N-terminal ubiquitylation / ubiquitin-mimic conjugation Ub- Used to model ubiquitin-linked biology or to create defined peptide–protein conjugates (method is project-dependent; share your target linkage).

Best pick (charge/recognition study): Me2- or Me3-. Best pick (protein-conjugate biology): Ub- (project-dependent linkage).

N-terminal conjugation (PEG, lipid, biomolecule) orientation-controlled conjugates
N-terminal PEGylation N-terminal lipidation biomolecule conjugation carrier proteins
Conjugation type Abbrev. Primary function / why it’s used
N-terminal PEGylation PEG- Increases hydrodynamic radius; often improves solubility and can extend half-life (project-dependent).
N-terminal lipidation (e.g., palmitoylation, myristoylation) Palm- / Myr- Enhances membrane interaction and albumin binding; commonly used for PK enhancement and delivery constructs.
N-terminal protein/carrier conjugation (project-dependent) Peptide–KLH / Peptide–BSA Immunogens and assay reagents; N-terminal attachment can control epitope presentation and loading consistency.
N-terminal oligonucleotide conjugation (project-dependent) Peptide–DNA / Peptide–RNA Delivery and targeting constructs; N-terminal attachment controls orientation and reduces multi-site mixtures.
N-terminal small-molecule payloads (project-dependent) Peptide–payload Targeting/probe constructs; handle selection preserves the peptide pharmacophore and payload activity.

Best pick (PK / exposure): N-terminal PEGylation or N-terminal lipidation—selected based on solubility, potency, and dosing goals.

Applications of N-terminal peptide modification

Imaging & detection
  • N-terminal fluorescent peptides (FAM/FITC, TAMRA, Cy dyes)
  • Radiometal chelation (DOTA/NOTA; project-dependent)
  • FRET and binding assays
Affinity capture & immobilization
  • N-terminal biotinylated peptides for pull-down
  • Surface immobilization with controlled orientation
  • Assay reagent standardization
Half-life & PK enhancement
  • N-terminal PEGylated peptides (project-dependent)
  • N-terminal lipidation (albumin binding; project-dependent)
  • Stability-oriented N-terminal capping
Modular conjugation workflows

Use click-ready N-terminus handles to connect peptides to probes, carriers, or delivery modules with high chemoselectivity.

  • SPAAC (azide + DBCO/BCN)
  • CuAAC (azide + alkyne; copper-tolerant workflows)
  • Late-stage functionalization
Biomolecule conjugates

N-terminal conjugation supports defined orientation for peptide–protein (carriers), peptide–oligo, and peptide–payload constructs.

  • Immunogens and carrier conjugates (project-dependent)
  • Peptide–oligonucleotide delivery constructs
  • Targeted peptide–payload hybrids

Workflow: design → synthesis → QC → delivery

Design review
  • Goal
  • Site constraints
  • Handle choice
Synthesis & modification
  • N-terminus
  • cap/label/handle/conjugate
Purification & QC
  • HPLC / UPLC
  • LC-MS (feasible)
  • COA
Delivery & documentation
  • Lyophilized peptide
  • HPLC / UPLC profile
  • LC-MS, as feasible

Figure: Practical workflow for N-terminal peptide modification from design selection to QC-backed delivery.

Quality control & typical deliverables

Standard QC
  • Analytical HPLC/UPLC purity profile
  • Identity confirmation (LC-MS when feasible)
  • COA + method summary
What we verify for N-terminal mods
  • Expected mass shift for selected N-terminus chemistry
  • Conversion / starting material check (project-dependent)
  • Purity aligned to intended application
When to add more

If your decision depends on stability, conjugation ratio, or release behavior, tell us up front—we’ll align analytics to the question you’re answering.

FAQ

What is the most common N-terminal peptide modification?

N-terminal acetylation (Ac-) is one of the most common: simple, broadly compatible, and often improves stability while reducing N-terminus charge.

Is N-terminal conjugation the same as peptide modification?

Yes. If a payload is attached at the N-terminus (PEG, lipid, dye, small molecule, oligo, protein/carrier), the peptide’s structure changes—this is an N-terminal peptide modification.

Should I choose N-terminal or cysteine-specific labeling?

Choose N-terminal labeling when you want a single defined site and the N-terminus is not required for function. Choose cysteine chemistry when you have one unique Cys and need a thiol-selective attachment point.

Can you add click chemistry handles at the N-terminus?

Yes. We support N-terminal azide/alkyne and copper-free partners (DBCO/BCN) for selective SPAAC or CuAAC workflows.

What do you need to start?

Send the sequence, desired N-terminal modification (or goal), quantity/purity, and intended use. If you need help choosing, tell us whether you’re optimizing for stability, detection, capture, or conjugation orientation.

Can you combine N-terminal modification with internal or C-terminal changes?

Yes. N-terminal modification is frequently combined with internal handles, PTM mimics, cyclization, or C-terminal amidation—when the design supports selective chemistry and a practical purification/QC plan.

More FAQ'sAll FAQ's

Contact & quote request

For the fastest quote, share your sequence(s), target N-terminal modification (or goal), constraints (free N-terminus required? disulfides? internal handles), quantity/purity targets, and intended application. We’ll recommend a practical synthesis route plus purification/QC aligned to your use case.

Fastest path
Request a Quote Review the library

What happens next: feasibility notes, recommended N-terminal strategy (cap/label/handle/conjugate), and a QC plan that confirms identity and purity for your application.

Fast quote checklist
  • Sequence(s) + terminal requirements (free vs capped)
  • Desired N-terminal modification (or objective: stability/detection/capture/conjugation)
  • Internal reactive residues (Cys/Lys/Tyr) + disulfides
  • Quantity (mg) + purity target
  • Intended use (assay, imaging, in vivo)

If you’re choosing between N-terminal vs side-chain labeling, tell us whether you need single-site homogeneity or whether multi-site labeling is acceptable—we’ll recommend the cleanest design.

Common add-ons (optional)
  • Extra purification (higher purity targets)
  • Orthogonal confirmation (project-dependent)
  • Custom packaging/aliquoting
Send with your request
  • Any restricted motifs (e.g., N-terminal required for activity)
  • Preferred handle chemistry (azide/alkyne/DBCO/BCN) if applicable
  • Known solubility constraints and preferred counterion/salt form
Talk to a chemist Request a quote

Recommended reading

Background reading on terminal modification, peptide labeling, and design considerations for site-defined chemistry.

  1. Review article (open access): PMC9508648

References are provided for background and do not imply endorsement by the publishers.

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