Our peptide synthesis service is optimized to help you rapidly progress your immunotherapy discovery. Peptides are synthesized using the latest solid and solution phase peptide chemistries and validated by in-process analytical checks to ensure sequences are representative of native epitopes, neoantigens and post-translationally modified proteins. All projects start with a bioinformatics review, MHC binding motifs are mapped, epitope immunogenicity is predicted and spacer/linker sequences optimized for proteasomal cleavage. Synthesis uses microwave accelerated Fmoc chemistry, cycle times are fast, coupling efficiency is monitored by in-process UV, and products are purified to >98 % by preparative RP-HPLC and confirmed by tandem mass-spectrometry. Final products are tested for endotoxin and bioburden and subject to accelerated stability studies to ensure quality, purity and shelf-life for both in-vitro T-cell priming and in-vivo adoptive transfer experiments. We typically prepare milligram and gram scale quantities of long peptides (>40 mer), cyclic constrained peptides to improve MHC-II presentation and phospho-peptides that mimic tumor-specific phospho-signatures. Clients can view the progress of their synthesis projects in real-time through a secure client portal where they can access synthetic progress, analytical data packages and regulatory-compliant documentation to enable a smooth transition to cGMP production. In addition to peptide synthesis, we have an immunology group that can formulate peptide pools and tetramers as well as validate peptides in humanized mouse models.
Fig. 1 Peptide therapy restores immune homeostasis via natural antigen-specific immunoregulatory pathways.1,2
Synthetic peptides are key enabling tools for immunotherapy: they make programmable immunity possible by connecting genomic discovery to actionable immune intervention. From viral defense to autoimmunity, almost no known 'off the shelf' reagent will target cryptic epitopes, conformational epitopes or post-translationally modified neoantigens driving tumor recognition, tolerance release, or pathogen neutralization with the flexibility or specificity required. However, by leveraging a partner that designs orthogonal purification, real-time analytics and regulatory foresight into every condensation step, your lab can have full confidence in the fidelity, traceability, and scalability of the molecular reagents it is using, enabling smaller and faster feedback loops in vaccine development, T-cell probing and biologic lead optimization.
Immunoassays are very sensitive to very small amounts of contaminants that may be immunostimulatory because they mimic neo-epitopes or inhibitory because they suppress dendritic-cell maturation by mimicking endotoxin. The purity is therefore a continuous optimization variable in the synthesis rather than a final specification parameter. Solid-phase peptide synthesis is carried out on resins and linkers specifically selected to minimize racemisation and deletion. Counter-current washings are used after each step to remove truncated sequences before they have a chance to proliferate. Cleavage and deprotection under scavenging conditions to prevent alkylation by reactive cations is followed by orthogonal chromatography. Reversed-phase, ion-exchange and size-exclusion steps separate, respectively, hydrophobic variants, charge isoforms and aggregates. A suite of in-line UV, fluorescence and light-scattering detectors creates a multi-dimensional fingerprint that is recorded in an electronic birth certificate of every batch produced. Endotoxins are removed by membrane adsorption and ultrafiltration techniques that have been validated for molecular weight cut-offs that are selective against peptides while depleting lipopolysaccharide. The product is therefore a peptide reagent whose immunological response is due to the epitope rather than contaminants, thus allowing a mechanistic interpretation.
Native epitopes are often post-translationally modified to control MHC affinity or conformational stability, a detail which is generally lost from off-the-shelf catalogues. In order to fill this gap, we have introduced a number of chemoselective and orthogonal modifications to our synthetic toolset. These include site-specific phosphorylation, chemoselective cyclisation, and tunable PEGylation, all introduced using protecting-groups which remain stable during iterative coupling cycles, but can be removed cleanly and under mild, aqueous conditions. Phosphorylated serines and threonines are introduced using mono-benzyl phosphoramidites whose benzyl ethers can be globally removed without β-elimination. Side-chain directed, head-to-tail cyclisation is achieved using N-terminal anchoring groups that can be cleaved to release the N-terminus for on-resin lactamization of the full-length sequence. Such conformationally constrained scaffolds can help recapitulate the bioactive conformation of native receptor-bound peptides, as well as provide proteolytic stability. PEGylation can be introduced at user-defined sites using orthogonal click handles that can be used to attach mono-disperse PEG polymers, in order to tune the hydrodynamic radius and in-vivo half-life, without disturbing the antigenic core. Intact-mass, NMR conformational analysis and functional validation (as evidenced by T-cell receptor or antibody recognition) confirm the identity of each bespoke peptide variant, which are ideally suited to tasks such as defining signalling thresholds, building supramolecular vaccines or fine-tuning pharmacokinetics.
Synthetic peptides are powerful molecular probes that can be used to validate putative epitopes prior to protein expression. Sequences with defined purity and modification status, are produced and delivered, obviating concerns about cross-reactivity, batch to batch variability, and the intellectual taint that can be associated with iterative animal immunizations. Libraries of overlapping peptides containing single amino acid mutations or post-translational modifications can be interrogated in ex-vivo human T cell assays to rapidly confirm minimal epitopes and anchor positions. For personalized neoantigen vaccines, it is possible to synthesize libraries in days after tumor sequencing, allowing for a bedside to bench workflow that can be iterated upon to keep up with tumor clonal evolution. The incorporation of click handles or lipid tags on the peptides that are being assembled onto a nanoparticle or self-adjuvanting micelle scaffold can streamline rapid conjugation that obviates protracted conjugation optimization steps. In addition, consideration of regulatory requirements is built into the early process design: synthetic routes are vetted to remove animal-derived reagents, the potential fate of impurities are known relative to ICH guidelines, and stability data to support long-term storage and clinical trial stability is generated early. In sum, these design choices condense the timeline from epitope nomination to IND ready materials, and inject confidence that genomic discoveries can be quickly translated into immune-modulatory therapeutics.
In both cancer and infectious-disease settings, synthetic peptides have transitioned from being inert reagents to customizable instructions for the immune system. Peptides can mimic tumor-specific neoantigens, infectious disease-derived epitopes or model recall antigens with sufficient fidelity to allow for mechanism elucidation, vaccine priming, and long-term immune monitoring all in a single framework.
The landscapes of patients' mutations, and the peptides they encode, are unique to each individual and the source of peptides which do not exist in healthy cells/tissues. With synthesis of sufficient site-specific purity, neoantigen peptides can act as strong non-self danger signals. The workflow starts with in-silico prioritization pipelines that combine HLA-binding predictions, clonal abundance scores, and immunogenicity predictions to select a small, immunologically representative set of peptides. The selected peptides are synthesized with a high degree of purity and appropriate post-translational modifications (if available), such as phosphorylated or deamidated residues, when present in the source tumor. Each candidate is purified (removing truncated and racemized impurities) and endotoxin depleted, to allow for pulsing of dendritic cells or direct conjugation to nanoparticles. The peptides are tested for stability with lyophilization and reconstitution and long-term storage to assure their physiochemical stability from the compounding pharmacy to the patient bedside. The peptides can then be used clinically as synthetic long peptide vaccines, or complexed to RNA-lipoplexes, or can be used as dendritic cell cargo, and in each case are formulated to also co-deliver appropriate adjuvant signals to promote poly-functional and tumor reactive T cell clones. Patient-specific lots are released to clinic based on identity (mass-spectrometry) and potency (bioassays) data.
Designing vaccines that target viral, bacterial or parasitic pathogens in a rational way requires panels of epitopes which include both conserved and variable (strain-specific) epitopes. We design and prepare overlapping peptide sets to cover whole proteomes or specific immunodominant regions with identical lengths, amidation and purity (batch-to-batch consistency). Chemical modifications can be added post-synthetically in a site-specific manner (lipidation to provide membrane anchoring, cyclisation to lock a conformation, glycosylation to present a 'natural' virion surface). All peptide libraries are supplied with fully digitized QC files for retention-time fingerprints, mass spectra and endotoxin clearances to facilitate transfer from the animal facilities to the clinic. Adjuvant compatibility testing is done on all peptides as part of the process to ensure that peptide-excipient interactions do not compromise immunogenicity and accelerated stability under thermal and oxidative stress can be provided to predict shelf life under a range of global distribution scenarios. These epitope libraries have been used to measure cross-reactive T-cell breadth in response to influenza drift, to confirm the conservation of epitopes in coronavirus spike proteins and to prioritize candidates for pan-filovirus or universal flavivirus vaccines.
Longitudinal monitoring of antigen-specific immune responses necessitates peptide reagents that are identical and consistently active between different time points. We produce lyophilised peptide pools that can be used for intracellular cytokine staining, tetramer flow cytometry or multiplexed Luminex bead-based assays. Each peptide comes with a digital certificate of analysis (i.e., unique synthetic lot linked to retention-time, mass-spectral and bioactivity signature) that ensures the traceability of antigen-specific immune data, removing interpretational bias when integrating datasets from different clinical sites or time points. We custom barcode and robotically aliquot peptides to reduce freeze-thaw cycles, and control endotoxin carryover from packaging materials to protect primary cell cultures. For discovery-based applications, high-density peptide microarrays allow unbiased visualisation of epitope spreading during checkpoint-inhibitor immunotherapy or after viral infection. We also provide reference standards for assay normalisation, stored in duplicate under separate cryopreservation conditions, to calibrate changes in sensitivity or specificity over time, and thus maintain the internal consistency of immune-monitoring stories between phase I dose-escalation and phase III clinical endpoints.
From concept-to-crystal we turn ideas into well-defined molecules by tightly integrating the design, curation, and quality assurance steps into a continuous process. Our workflows are optimized for discovery or GMP final-stage supply, adapting the rigor, data depth, and release model to the conceptual and regulatory phase. The outcome is a set of peptide reagents that are guaranteed to have maintained structural integrity and provenance throughout the translational journey without having to be re-qualified or re-invented.
The peptide library ranges from the small sequence motifs based on dipeptides to the long peptide chains, which get into the size range of small proteins. The convergent solid-phase synthetic protocols combine segment condensation and on-resin chemistry. They are used to avoid the aggregation issues, which are frequently met during the synthesis of long sequences. Side-chain specific functionalities, such as phosphorylated residues, lipidated cysteines or non-canonical amino acids, can be introduced in the peptides using orthogonal protecting-group strategies while maintaining the stereochemical fidelity during the iterative coupling steps. In addition, appropriate folding strategies are included in the post-synthesis treatment to ensure that the disulfide connectivity and the secondary structure elements of the peptides are as close as possible to the reference protein. The information about sequence, topology and design strategy are summarized in a digital design dossier for each peptide, which correlates the synthetic pathway with the predicted physicochemical properties. If necessary, based on the evaluation of the biological properties, e.g. immune assays or pharmacokinetics, the design can be easily adapted to provide shorter truncations or different termini within days. The reagent modules that are used to design the peptide library also allow parallel synthesis of peptide families, such as overlapping scanning libraries, substitution matrices or conformational mimics, within a short time without loss of individual quality.
Ambition and regulation do not march in lockstep; it's more useful to think of our processes as sliding along a spectrum of control, rather than flicking a "switch". Our "research" peptides are manufactured under conditions that focus on speed and flexibility, but still include built-in identity and endotoxin removal steps that are adequate for use with cell cultures or animal studies. Peptides for GMP or clinical use are made in a GMP suite, with classified cleanroom, gowning procedures and digital batch records all preconfigured to ease the visit of an international auditor. Raw materials are sourced with documentation for the lack of animal-derived byproducts, solvents are monitored for elemental impurities, and every step is supported by risk-analysis documentation that addresses different regulations. The need for re-validation is removed from the research-to-GMP transition - the sequences, analytical procedures and release criteria simply move from one context to another without delay. Phased transition is also an option for those who want to defer GMP activation until a clinical decision point is reached.
Quality attributes, in particular structural integrity, are validated by a series of orthogonal assays, not a single check-point. HPLC, including reversed-phase chromatography for all hydrophobic isoforms and deletion species, which are separated in a gradient using a range that approximates physiological conditions, is conducted using ion-exchange and size-exclusion chromatography to understand charge isoforms and aggregation. Mass spectrometry analysis, including intact mass, peptide mapping, fragmentation and high-resolution isotopic profiles, confirms elemental composition and positions of post-translational modifications to within a single residue. Other analytical methods, such as circular dichroism for secondary structure confirmation or fluorescence for understanding the microenvironment around aromatic residues, can be used to further support the structure of the purified protein and to link chromatographic purity to conformational fidelity. An electronic archive of all analytical data, with revision tracking and electronic signatures, is maintained as a cloud-based document that can be used for direct submission or disclosure to regulatory agencies or the scientific community at large. As an independent reference standard, previously stored under redundant cryopreservation conditions, is used as a control against which future lots are compared to ensure that analytical reports and conclusions are internally consistent over the course of longitudinal studies or multi-site clinical trials.
Immunotherapy development requires peptides that meet precise structural, purity, and modification requirements to ensure reliable results. Our custom peptide synthesis services cover simple linear peptides to complex modified versions, supporting discovery and translational research. Each peptide undergoes stringent analytical validation to meet research or regulatory standards. With scalable production and fast turnaround, we provide tailored peptides that accelerate breakthroughs in cancer immunotherapy, vaccine development, and autoimmune research. Our synthesis expertise ensures accuracy, quality, and flexibility for your project's success.
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Peptide Synthesis Services at Creative Peptides
Peptide synthesis is at the heart of modern immunotherapy development. Our services deliver peptides tailored to your needs with unmatched precision and reliability. Contact us today to request a custom quote and transform your immunotherapy research into clinical success.
1. What peptide lengths can you synthesize?
We synthesize peptides up to 120 amino acids.
2. Do you provide GMP-grade peptides?
Yes, GMP-grade peptides are available for clinical trials.
3. Can you include modifications?
Yes, modifications include PEGylation, cyclization, lipidation, and more.
4. How is quality assured?
HPLC and MS validation ensure peptide integrity.
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