Phosphorylated Peptide Synthesis / Phosphopeptides

Site-defined pSer, pThr, and pTyr peptides (including multi-site phosphorylation) with purification and analytics that confirm identity and purity.

Custom phosphopeptide synthesis for kinase and phosphatase assays, signaling biology, phospho-specific tools, and phosphoproteomics standards.

Overview

What are phosphorylated peptides (phosphopeptides)?

Phosphorylated peptides—also called phosphopeptides or phospho-peptides—are peptides that contain one or more phosphate groups installed at defined residues, most commonly serine (pSer), threonine (pThr), or tyrosine (pTyr). A single phosphorylation adds ~+79.966 Da (HPO3) and introduces strong negative charge, which can meaningfully change conformation, binding, and assay behavior.

Bio-Synthesis provides custom phosphorylated peptide synthesis using robust SPPS workflows and route planning aligned to your goals. We routinely produce mono- and multi-phosphorylated peptides, as well as paired phospho/non-phospho controls for kinase studies, phospho-specific antibody projects, and LC–MS workflows.

pSer peptide pThr peptide pTyr peptide multiphosphorylated peptides ISO 900:2015/ISO13485:2016 45+ Years of Expertise U.S. Facilities - Texas
Phosphopeptides model phosphorylation on and off states for signaling, binding, and enzyme assays. ON state shows phosphorylated peptide enabling kinase-driven signaling and target protein binding; OFF state shows non-phosphorylated peptide with no binding after dephosphorylation.

Figure: Phosphopeptides model phosphorylation “on/off” states for signaling, binding, and enzyme assays. Kinase-mediated phosphorylation activates interactions, while phosphatase-driven dephosphorylation switches signaling off.

Exact site control

Defined residue-level phosphorylation helps avoid mixtures and supports clean interpretation.

Assay-relevant behavior

Charge and recognition motifs can shift binding, enzyme kinetics, and chromatography.

Analytics that matter

We align purification and QC to your intended use (screening, MS standards, antibody work).

Related services: Peptide Modifications, Isotope-Labeled Peptides, Difficult Peptide Synthesis.

Why protein phosphorylation is important

Phosphorylation is a universal regulatory “switch”

Protein phosphorylation is one of the most common post-translational modifications (PTMs). It is installed by kinases and removed by phosphatases, enabling rapid regulation of protein activity.

  • Activity control: turns enzymes on/off or tunes catalytic rates
  • Conformation: changes folding or local structure, exposing/occluding sites
  • Localization: creates signals for trafficking and compartmentalization
  • Interactions: creates binding motifs (e.g., for SH2/PTB domains) and alters networks
Why phosphopeptides are indispensable tools

Because phosphorylation is dynamic in cells, many experiments require defined phospho-states that biology does not easily provide. Phosphopeptides let you isolate the “phosphorylated region” and test it directly.

  • Kinase substrates and inhibitor screening panels
  • Phosphatase specificity and dephosphorylation kinetics
  • Phospho-dependent binding (adaptor domains, signaling modules)
  • Phospho-specific antibody validation and epitope mapping
  • LC–MS standards for phosphoproteomics method development
Key benefit: controlled biology in a defined molecule

Phosphorylation can encode “barcodes”—combinatorial patterns that change function. For complex signaling regions, multi-site phosphopeptides allow controlled experiments that compare specific phosphorylation patterns side-by-side.

Signal switching

Phosphorylation can turn interactions “on/off” by changing charge and conformation, rewiring binding and activity.

Pathway mapping

Defined phosphopeptides enable kinase/phosphatase assays and motif mapping without full-length proteins.

Assay confidence

Phospho-specific antibodies and enrichment workflows perform best with validated phosphopeptide controls.

Available Synthesis Strategies for Phosphorylated Peptides

High-purity phosphorylated peptides (phosphopeptides) demand site control plus a synthesis route that protects the phosphate group, avoids side reactions, and preserves sequence integrity. We routinely support single-site and multi-site phosphorylation projects.

1) Building-block incorporation (preferred)

Use protected phospho-amino acid building blocks during SPPS for site-defined pSer/pThr/pTyr insertion.

  • Highest control over phosphorylation site(s)
  • Best for multi-site phosphopeptides
  • Minimizes heterogeneity vs post-synthetic methods
2) Post-assembly phosphorylation

When appropriate, phosphorylation is introduced after chain assembly to fit sequence constraints or project design.

  • Useful for certain motifs or workflow constraints
  • Feasibility depends on residue context and selectivity needs
  • Defined acceptance criteria for conversion & purity
3) Strategy upgrades for difficult phosphopeptides

Multi-phosphorylation can increase acidity and reduce coupling efficiency. We tune chemistry and workflow to maintain yield and purity.

  • Aggregation control & backbone disruption (as needed)
  • Stepwise optimization for problematic junctions
  • Purification strategy aligned to phosphate state(s)
How we choose the best route

We select a practical strategy based on your phosphorylation pattern (single vs multi-site), sequence behavior (aggregation/solubility), and the role of the phosphate group (binding epitope vs functional mimic). If your project requires strict isoform control, we prioritize building-block incorporation to enforce site definition.

Related: Difficult Peptide Synthesis · Peptide Modifications · Isotope-Labeled Peptides

Available Phosphoryl Groups We Provide

Bio-Synthesis routinely prepares custom phosphorylated peptides (phosphopeptides) with one or multiple phosphate groups. The most common biologically relevant sites are Ser, Thr, and Tyr.

Phosphoserine (pSer, pS)

Core modification for kinase pathways and binding motifs; common in signaling and regulatory domains.

  • Single or multi-pSer patterns
  • Compatible with comparative “non-phospho” controls
  • Purification/QC aligned to phosphorylation state
Phosphothreonine (pThr, pT)

Frequently used for kinase substrate studies and functional motif mapping.

  • Site-defined pThr insertion
  • Multi-site combinations with pSer/pTyr
  • Design support for sterically constrained regions
Phosphotyrosine (pTyr, pY)

Key signaling handle for SH2/PTB interactions; used in binding assays and phospho-specific antibody validation.

  • Defined pTyr placement
  • Excellent for interaction mapping & antibody tests
  • Fit-for-purpose QC and documentation
Multi-site phosphorylation (custom patterns)

We support peptides containing multiple phosphoserines, multiple phosphothreonines, multiple phosphotyrosines, or mixed combinations (e.g., pS/pT, pS/pY, pT/pY). Multi-site designs are especially useful for pathway-relevant motifs, kinase docking regions, and phosphoproteomics standards.

single-site phosphopeptides multi-site phosphopeptides pSer / pThr / pTyr combinations phosphopeptide controls

Phosphopeptide synthesis services (what we make)

Expand the options below for common phosphopeptide types, typical use-cases, and design notes. Feasibility depends on sequence behavior, phosphorylation pattern, and downstream assay requirements.

phosphoserine peptide phosphothreonine peptide phosphotyrosine peptide phosphopeptide synthesis
Type Typical notation Common use Design notes
Mono-phosphorylated pS, pT, pY Kinase substrates; phospho-specific binding motifs Pair with non-phospho control (Ser/Thr/Tyr) and optionally a phosphomimetic (Asp/Glu).
Di- / tri- phosphorylated pS/pT/pY combinations Combinatorial signaling patterns; “barcode” studies Route planning and mild deprotection conditions can reduce side reactions and improve yield.
Tyrosine-rich motifs pYxxP, ITAM-like, SH2/PTB motifs Adaptor domain binding and recruitment studies Spacing around pY often matters; we can help design peptides that preserve recognition context.
Ser/Thr-rich motifs pS/pT in acidic clusters Kinase motif mapping; priming phosphorylation studies High acidity can affect coupling and purification; consider length and flanking residues.

Tip: If your goal is enzyme kinetics, include flanking residues that match the natural sequence context (often improves specificity).

phosphopeptide controls paired peptides phosphomimetic
  • Matched phospho/non-phospho pairs (same sequence) for clean comparisons
  • Site mutants (S/T→A; Y→F) to confirm phospho-dependence
  • Phosphomimetics (S/T→D/E) when a stable “negative charge mimic” is desired
  • Isotope-labeled phosphopeptides for LC–MS quantitation standards (on request)

See also: Isotope-Labeled Peptides

non-hydrolyzable phospho pTyr analogs custom evaluation

Some programs require phosphatase-resistant or otherwise specialized analogs to stabilize a phosphorylation state. If you have a target analog or literature precedent, share it—our team will evaluate feasibility and propose a route.

  • Phosphatase-resistant analogs (project-dependent)
  • Special residue constraints (e.g., additional PTMs, labeling, biotin/handles)
  • Multi-modified constructs (phospho + label + linker), evaluated case-by-case
Keyword coverage & scope

This page targets: phosphorylated peptide synthesis, phosphopeptide synthesis, phosphorylated peptides, phosphopeptides, phosphoserine peptide, phosphothreonine peptide, phosphotyrosine peptide, multi-phosphorylated peptides, and custom phosphopeptide synthesis.

What phosphorylated peptides are used for

Kinase assays

Substrate peptides, motif mapping, inhibitor screening, and specificity profiling.

  • Phospho and non-phospho matched sets
  • Panel designs for screening
  • Optional labels/handles for readouts
Phosphatase assays

Define dephosphorylation kinetics and substrate preferences.

  • Single vs multi-site comparisons
  • Motif-dependent activity studies
  • Assay-friendly purification options
Phospho-dependent binding

Capture and quantify interactions that require phosphorylation.

  • SH2/PTB and adaptor binding motifs
  • Pull-down or SPR/BLI studies
  • Biotin/handles if needed
Phosphoproteomics & LC–MS standards

Phosphopeptides are commonly used as standards and controls during method development, enrichment validation, and quantitative workflows. If your use-case is quantitation, we can evaluate isotope labels and matched light/heavy sets.

  • Method development and retention benchmarking
  • Enrichment workflow checks (project-dependent)
  • Absolute or relative quantitation designs
Antibody validation & epitope mapping

Phospho-specific antibodies must distinguish phospho from non-phospho epitopes. Defined phosphopeptides enable direct validation.

  • Matched phospho/non-phospho controls
  • Point mutants for specificity confirmation
  • Peptide panels for epitope mapping

Design guidance (how to get a robust phosphopeptide)

Two synthesis routes: building-block incorporation vs post-assembly phosphorylation

Site-defined phosphopeptides are most commonly made by incorporating protected phospho-amino acids during SPPS. In some designs, post-assembly phosphorylation may be considered—but it often requires more optimization to avoid mixtures. If you tell us your sequence and goals, we’ll recommend the most reliable approach.

Building-block incorporation (typical)
  • Highest confidence in site definition
  • Works well for mono- and many multi-site designs
  • Enables matched sets and systematic libraries
Post-assembly phosphorylation (case-by-case)
  • May fit certain scaffold designs
  • Can require extensive optimization for selectivity
  • Used when building blocks are impractical
Common challenges (and how we manage them)
Challenge Why it happens Practical mitigation
Multi-site acidity Multiple phosphates increase negative charge and can reduce coupling efficiency. Route planning, coupling optimization (reagents/stoichiometry), and careful selection of deprotection conditions.
Side reactions (e.g., β-elimination) Certain conditions (especially harsh base/temperature) can promote elimination at phospho-Ser/Thr in some contexts. Milder, controlled deprotection/coupling parameters near phospho-residues; minimize exposure to unnecessary harsh conditions.
Purification complexity Phosphorylation alters polarity and may create closely eluting species. Method development (gradient, ion pairing, pH) aligned to your acceptance criteria and intended use.
Analytical ambiguity Intact mass confirms phosphorylation but not always site position in multi-site constructs. Add optional MS/MS site confirmation when your project needs explicit site assignment.

If your sequence is also aggregation-prone (hydrophobic clusters, long length, repeats), consider linking to Difficult Peptide Synthesis for strategy options.

Workflow: from sequence to phosphopeptide

Workflow: from sequence to phosphopeptide

Figure: Typical workflow for phosphorylated peptide synthesis—design review through purification, QC, and documentation.

Quality control & typical deliverables

Standard QC
  • Analytical HPLC/UPLC purity profile
  • Identity confirmation (LC-MS when feasible)
  • COA + method summary
Phospho-focused checks
  • Phospho/non-phospho profile review (method-dependent)
  • Optional MS/MS site confirmation (on request)
  • Batch-to-batch reproducibility for resupply
When to add more

If your decisions depend on exact site assignment in multi-site constructs, tell us early—we’ll align analytics to it.

FAQ

Phosphorylated peptide vs “peptide phosphorylation” — what’s the difference?

“Phosphorylated peptide” (phosphopeptide) refers to the final product you purchase and test. “Peptide phosphorylation” often refers to the biological process or enzymatic phosphorylation in assays. This page focuses on custom synthesis of defined phosphopeptides.

Which phosphorylation sites do you support?

We routinely synthesize pSer, pThr, and pTyr at defined positions, including multiple sites within a single peptide.

Why do multi-phosphorylated peptides sometimes take more optimization?

Multiple phosphate groups increase acidity and can reduce coupling efficiency, complicate purification, and increase sensitivity to harsh conditions. Multi-site designs benefit from route planning and controlled coupling/deprotection parameters.

Can you provide matched phospho/non-phospho controls?

Yes—matched sets are strongly recommended for kinase, binding, or antibody studies. We can also provide mutants (S/T→A; Y→F) or phosphomimetics (S/T→D/E) when appropriate.

How do you confirm the phosphorylation?

Typical confirmation includes analytical HPLC/UPLC and LC-MS (intact mass) when feasible. If you require explicit site confirmation (especially multi-site constructs), MS/MS can be added on request.

Do phosphopeptides require special handling?

Many phosphopeptides are more polar and may behave differently in HPLC and solubility. We provide reconstitution guidance aligned to your sequence and intended use.

What information do you need for a quote?

Send the peptide sequence, phosphorylation site(s) and residue type(s), quantity and purity target, and intended application. If you need matched controls or special analytics, include that as well.

Can you combine phosphorylation with other modifications?

Often yes (project-dependent). Common combinations include labels, handles, biotin, or isotope labels. Share your full design and constraints so we can propose a robust route.

Do you support phosphopeptide libraries or panels?

Yes. Libraries are common for kinase specificity profiling, motif scanning, and antibody epitope mapping. We can recommend panel design and consistent QC for comparability.

What purity levels do you offer?

Purity targets are set by your use-case (screening vs structural vs MS standards). We’ll recommend a realistic specification and purification plan aligned to your application.

Ordering guide: recommended specs by application

Phosphorylated peptides (phosphopeptides) are often used as assay substrates, binding motifs, or validated controls. The table below provides practical starting points. If your workflow is sensitive to batch-to-batch variation, ask for matched non-phosphorylated controls and sequence variants.

Typical use Common format Suggested purity Suggested amount Notes that affect success
Kinase / phosphatase assays 8–20 aa, 1 site (pS/pT/pY) ≥85–95% 1–10 mg Include a matched non-phosphorylated control. Consider N-terminal acetylation or C-terminal amidation if your native context is capped.
SH2 / PTB / 14-3-3 binding studies 10–30 aa, 1–2 sites ≥95% 2–20 mg Orientation and spacing matter; we can provide alanine mutants, Asp/Glu mimics (when appropriate), and length variants to map binding.
Phospho-specific antibody validation 12–25 aa, 1 site + controls ≥95% 1–10 mg Best practice: order phospho + non-phospho + nearby-site variants (e.g., pS vs pT) to prove specificity and rule out off-target binding.
LC–MS/MS phosphoproteomics standards 7–25 aa, defined site(s) ≥95–98% 100 µg–5 mg Ask for accurate mass + purity trace. For quant workflows, consider stable isotope labeling and matched light/heavy pairs.
Multi-site “barcode” phosphorylation 15–50 aa, 2–5+ sites ≥90–95% (project-dependent) 1–10 mg Multi-phosphorylated peptides can require strategy upgrades (double coupling, longer coupling, alternative resins/solvents, fragment approaches). Tell us the biological acceptance criteria early.

Not sure what to order? Tell us your downstream method (assay, antibody, LC–MS), and we’ll recommend a practical set (phospho + non-phospho + variants) and a QC plan aligned to it.

What to send for the fastest quote
  • Sequence + phosphorylation site(s) (mark pS/pT/pY positions)
  • Terminal state (free vs Ac-/NH2) and any additional modifications
  • Quantity (mg or µg) and purity target
  • Intended application (assay, binding, antibody, LC–MS)
  • Any constraints (solubility, aggregation, “must match native”)

If you have a kinase motif, substrate region, or UniProt residue numbering, include it—we can help translate that into an order-ready sequence.

How to compare phosphopeptide suppliers

Use this checklist to avoid “looks fine on paper” failures in assays.

  • Site-defined strategy: building-block incorporation vs post-assembly phosphorylation (and which your sequence needs)
  • Multi-site capability: demonstrated handling of 2–5+ phosphorylation sites with acceptable purity/yield
  • Phosphate stability know-how: deprotection/cleavage tuned to minimize side reactions
  • QC that matches use: HPLC/UPLC + LC-MS; optional orthogonal confirmation for critical projects
  • Matched controls: non-phosphorylated, mutants, and close-site variants offered as a set
  • Handling guidance: recommended reconstitution, pH limits, storage, and freeze–thaw advice

Bio-Synthesis is optimized for custom phosphorylated peptide synthesis (phosphopeptides) with defined sites, fit-for-purpose purification, and documentation that supports reproducibility.

Contact & quote request

For the fastest quote, send your sequence(s), phosphorylation site(s) (pSer/pThr/pTyr), desired quantity and purity, and intended use (kinase assay, binding, antibody, LC–MS). We’ll recommend a practical synthesis/purification plan plus fit-for-purpose QC.

Fastest path

What happens next: Our technical team reviews your request and responds with feasibility notes, recommended route options, a QC plan, and pricing.

Fast quote checklist
  • Sequence(s) + any constraints (e.g., must keep termini free/capped)
  • Phosphorylation site(s) and residue types (pS/pT/pY)
  • Matched controls needed? (non-phospho, mutants, phosphomimetics)
  • Quantity (mg) + purity target + intended use
  • Any special analytics required (e.g., MS/MS site confirmation)

Not sure what to request? Send the biological context (kinase/phosphatase target or pathway) and we’ll recommend a practical peptide design and QC plan.

Recommended reading

Selected peer-reviewed references on phosphorylation “barcodes,” multi-site phosphopeptide synthesis challenges, and practical strategies.

  • Accelerated Multiphosphorylated Peptide Synthesis (AMPS)
    Org. Process Res. Dev. (2022). DOI: 10.1021/acs.oprd.2c00164. Read
  • Multiphosphorylated peptides: importance, synthetic strategies, and challenges
    Org. Biomol. Chem. (2020). DOI: 10.1039/D0OB00499E. Read
  • Microwave-assisted approach for multi-phosphopeptide libraries
    Org. Biomol. Chem. (2019). DOI: 10.1039/C9OB01874C. Read

References are provided for background and design insight; Bio-Synthesis does not claim ownership of the cited works.

Why Choose Bio-Synthesis

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