Pepscan is an all-in-one partner in peptides, building on 25 years of experience in advancing and applying peptide expertise to facilitate clients in the development and production of peptides. At its end-to-end facility in Lelystad, the Netherlands, Pepscan offers a range of patented technologies, phage display capabilities, a lead-optimization array platform, and production facilities for R&D- to GMP-grade peptides, including libraries and neoantigen vaccines. Among its patents is the CLIPS technology, which locks peptides into active conformations.
With its epitope mapping service platform, Pepscan also supports biotech companies in developing their antibody pipelines. The underlying protein mimicry platform delivers binding insights, even in cases where other technologies, such as linear, fall short.
For more information please visit our website: www.pepscan.com Or contact us via email at [email protected]
Neoantigen Peptides for Personalized Medicine The usage of neoantigen peptides in cancer vaccines is a rapidly growing and highly promising therapeutic field in cancer treatment. Preparing neoantigen peptides demands the highest level of care and reliability in terms of "meeting the specifications" and on-time delivery to the patient. Owing to our through expertise in peptide chemistry and a proven track record in fulfilling and surpassing customer expectations, Pepscan knows what it takes to be a world-class partner in this area. Pepscan's Offering in Personalized Medicine:
High-quality peptides manufactured conform to GMP and with the ultra-fast delivery times required for personalized therapeutic vaccine application.
Robust synthesis validation fully-optimized synthesis protocols & purification procedures, stringent quality control, and timely delivery with worldwide shipping.
Fast and personal consultation by experienced peptide chemists.
Highly trained staff with years of experience in peptide synthesis, design, stability, structural optimization, and molecular recognition of peptides.
Benefit from an unprecedented choice of library sizes, formats, and synthesis scales
Peptide libraries are widely applied as a powerful tool in biological research. They provide a rapid and cost-effective solution for a broad range of bioactivity-screening purposes, identifying critical bioactive peptides. Dedicated libraries of small peptides are ideal for T-cell epitope mapping & searching. Overlapping linear peptide libraries provide a quick route to mapping of the linear or complex epitope of your antibody. Peptide libraries are also used in biochemical studies as enzyme substrates, ligands or inhibitors.
Pepscan is the founder of peptide library technology and has over 25 years of experience in designing, synthesizing, and using custom peptide libraries. We provide our vast client base with:
Custom Library Synthesis and Delivery
Pepscan offers custom peptide arrays in all sizes and formats, ranging from a small set of peptides to libraries of 1,000’s of different species. Peptide lengths usually range from 5 to 30 amino acids, which is sufficient for most applications. However, as the inventor of the peptide library concept, Pepscan also supplies peptide libraries of up to 50 amino acids in length, if required with conformational constraints or post-translational modifications. Peptide libraries are manufactured on Pepscan’s state-of-the-art synthesis platform, usually at 4 μmol scale. This typically yields 1 to 4 mgs of crude peptide, ideal for fast and efficient screening work. Additional QC is available upon request. Typically, synthesis starts within days of order placement, with standard delivery times of around 3-4 weeks, depending on library size and peptide length. Custom peptide libraries are delivered as freeze-dried peptides in either 96-well plates for high-throughput screening or in individual microtubes. All peptides in the library will be delivered as TFA-salts as lyophilized powders.
Upon request, we produce peptide libraries with different structural modifications, such as N-terminal acetylation, biotinylation, Ser/Thr-phosphorylation, N-methylation, or labeling with fluorescent dyes. Please contact us for further information about custom modifications.
Create Your Own Library: Choosing the Right Library Design
At Pepscan, we have been designing, synthesizing and applying peptide array technology for many years. You can tap into this knowledge by using our free design assistance service. We provide recommendations to create the most efficient and economical library design and help you to compute lists of peptide library sequences. When the 3D-conformation of your peptide is crucial, we also offer unique libraries of 3D-constrained (CLIPS) peptides. A range of library design options are available (overlapping, truncated, T-cell truncated, alanine scan, replacement analysis, combinatorial positional scan, scrambled), each tailored to address specific research questions.
Please feel free to contact our experts for advice in designing your optimal peptide array. If your library has already been designed by yourself, just send us a quote request with an Excel file containing the peptide sequences and we will check them for feasibility.
For more information please visit; https://www.pepscan.com/custom-peptide-synthesis/peptide-libraries/
Expertise and equipment for up to 100 gram scale synthesis of peptides
When a peptide-based R&D program progresses successfully, at some point large(r) quantities of certain peptides will be required to advance a project to the next phase in development. To address this need, Pepscan offers a large scale peptide synthesis service. This allows us to work with you to progress your peptide project through the stages of development.
Peptide synthesis at large(r) scale involves far more than simply increasing the quantities of the materials to be used in the peptide synthesis process. True scale-up requires de novo protocol development to ensure the large scale synthesis of the peptide, at the requested quality and against economically feasible costs. With over 20 years of experience, our expert chemists will work to realize a smooth scale-up from first protocol design to final product delivery.
Our large scale peptide synthesis service retains all of the features that are also typical for our standard custom peptide synthesis service, such as guaranteed high purity and high synthesis success rate. Furthermore, preliminary cost analysis, thorough project review, process optimization, and detailed QC reports are part of our approach to ensure the successful and efficient delivery of your peptides.
Serving life sciences research with a comprehensive range of peptide modifications
Pepscan offers one of the most comprehensive peptide modification services currently available. With over 25 years of practical peptide synthesis and research experience, we have developed specific skills and expertise for making modified and difficult-to-synthesize peptides in excellent quality. Our highly skilled and committed scientific staff ensures that the most appropriate methods and techniques are selected for every custom peptide project. With a diverse range of modifications available for peptides, Pepscan routinely meets our clients’ specifications with unusual, custom-modified peptides, made on time and on budget. The exceptional quality and reliability of our peptide modifications service has been appreciated by customers worldwide for many years. Our peptide modification services include, but are not limited to the ones listed in the menu.
Additional modifications not listed here are available upon request, please inquire.
Providing solutions for all peptide needs to a global customer base
Pepscan provides a full spectrum of high quality custom peptide services that ranges from peptide synthesis and peptide modifications to high-throughput synthesis and screening of peptide libraries.
With over 25 years of expertise in custom peptide synthesis, Pepscan is a leading global producer of high-quality synthetic peptides. We have successfully synthesized 100,000’s of custom peptides for biotech and large pharma companies as well as academic customers. Pepscan consistently meets the highest standards for quality, custom service, and technical expertise. Custom peptide production is carried out under ISO 9001:2015 quality management using a range of state-of-the-art instruments in our 1,500 m² facility. With highly skilled and committed chemists we are fully capable of meeting the ever-increasing peptide needs in biology and drug discovery research. Pepscan has built unrivalled expertise in complex, constrained, multimeric or other special peptides you may need. Our customer support team is happy to assist in selecting the most appropriate peptide specification for your application, including peptide purity, amount and modifications.
With Pepscan’s custom peptide synthesis services you may rely on:
Peptide synthesis at Pepscan
Peptide synthesis at Pepscan is performed using state-of-the-art solid phase technologies. We exclusively apply Fmoc-based chemistries in automated peptide synthesizers and make use of rigorously optimized peptide synthesis protocols.
Whereas optimized synthetic strategies and purification procedures are of major importance for obtaining high quality peptides, the use of Ultra-high Performance Liquid Chromatography (UPLC) equipment combined with stringent analytical conditions is equally important. As an ISO 9001: 2015 certified provider of quality custom peptides, Pepscan relies on ‘high-end’ Waters Acquity UPLC systems to verify the purity of its peptides. The value of this highly sensitive analytical equipment is demonstrated in the case example below.
Peptides are supplied either as crude products or as HPLC-purified material (>70%, >85%, 90% or >95% purity), all dependent on the customers wishes, and in quantities of several milligrams up to 100 grams.
Each synthetic peptide is delivered as lyophilized white powder, with a certificate of analysis containing all relevant analytical data (ES-MS mass spectrometric details, reversed-phase UPLC-profiles).
Additional analyses (e.g. amino acid analysis, presence of residual solvents (mainly ACN, TFA) and water, stability determination) are optional. Upon request, peptide deliveries can be aliquoted in separate vials in a broad range of quantities (e.g. 10, 5, 1, 0.25 or 0.10 milligrams). Peptides and peptide libraries can also be delivered in microtiter plates suitable for high-throughput screening.
A highly effective lead discovery & optimization engine for linear and CLIPS-constrained peptides
HiSense is the name for Pepscan’s ultrasensitve array platform for identification and optimization of peptide leads. It is based on spatially defined, high-throughput synthesis of peptides on a solid support (455 wells polypropylene cards). The linear peptides can subsequently be transformed into conformationally constrained CLIPS constructs peptides. Binding of the target (protein, antibody) to the individual peptides can be determined via an ELISA-type read-out, to ultimately identify those CLIPS-peptides that sufficiently represent the protein interaction site of interest.
The HiSense lead optimization process
The lead optimization process involves chemical modifications of a lead peptide in order to improve potency, selectivity or pharmacokinetic parameters. It allows identifying those amino acids in the lead sequence that are essential to binding, as well as the amino acids that result in affinity improvement. In particular, the use of non-natural amino acids in our HiSense-arrays further extends the horizon for exploring new NCE’s beyond the reach of phage-display type libraries that solely rely on the use of natural amino acids.
The HiSense platform has successfully been used to identify (small) peptide binders designed/derived from whole protein sequences, and to create constrained (e.g. CLIPS) derivatives of lead sequences with significantly improved binding activity. We demonstrated in several projects that by applying the CLIPS/HiSense platform technology to selected peptide leads the affinity is increased by orders of magnitude (easily 1000 fold) and hence the bioactivity is strongly improved. As a result, this may lead to the generation of New Chemical Entities (NCEs) and thus opens novel options for IP-protection of existing peptide drugs.
Antibody discovery with synthetic peptide antigens that mimic complex targets
A major stumbling block in therapeutic antibody discovery is often the inability to generate potent antibodies, especially when the target antigen is complex in nature (GPCR’s, ion-channels) and cannot be obtained as a structurally intact protein. Pepscan’s unique and proven protein mimicry technologies provide an elegant and effective way to arrive at superior antigens for monoclonal antibody generation, in particular against these complex targets. Pepscan’s approach for the generation of antibodies is based on gaining structural knowledge of the target protein and the subsequent synthesis of CLIPS peptide-based immunogens.
Our successful development of antibody therapeutics relies on the ability to:
Our cutting-edge technologies are specifically designed to reconstruct such structurally complex binding sites and the platform has shown to be compatible with the well established antibody generation methods such as hybridoma and phage display.
Pepscan’s approach enables access to targets that is not easily accessible using conventional methods, and therefore unlocks the full potential of this target class for antibody therapeutics. In addition it allows tailoring antibody response to certain GPCR domains and hence to engineer antibodies which fulfill certain biological requirements. Pepscan’s approach has meanwhile resulted in several proprietary monoclonal antibodies in preclinical development, and in successful antibody discovery partnerships with leading pharmaceutical companies.
Defining linear, conformational and discontinuous epitopes: accurate, fast and cost-effective
The exact definition of antibody epitopes is important for various reasons, such as:
The surface of a protein interacting with an antibody is not always a simple string of amino acids, but often consists of a complex of loops and folds determined by the interaction between side chains of the residues.
Epitopes can be therefore classified in three types:
Daratumumab, Ofatumumab and Obinutuzumab approval via CLIPS Epitope Mapping
The vast majority of therapeutic antibodies have a conformational or discontinuous epitope. Therefore Pepscan, as the inventor of epitope mapping with linear peptides, perfected its technology through the addition of CLIPS technology to enable addressing the 3D spatial conformation of epitopes. This has resulted in CLIPS Precision Epitope Mapping, a unique, high resolution mapping technology using 3D-structured peptides to characterize discontinuous and conformational epitopes with high accuracy. Many leading companies, therefore, apply our Precision Epitope Mapping to their promising therapeutic antibodies, several of which received FDA breakthrough status or accelerated approval, such as daratumumab (JNJ), ofatumumab (GSK/Novartis) and obinutuzumab (Roche).
Precision Epitope Mapping is characterized by a number of unique features and benefits:
CLIPS Precision Epitope Mapping uses arrays with large, surface-immobilized libraries of conformationally CLIPS-constrained peptides derived from the target protein. The binding of the antibody to each peptide construct of the entire library is determined. This affinity information is used in iterative screens to define the sequence and conformation of epitopes in detail.
For more information please visit; https://www.pepscan.com/epitope-mapping-services
More than antibodies alone: elucidating protein-protein complexes at a high resolution
All antibodies are proteins, but not all proteins are antibodies. Understanding how proteins interact on a residue level is essential during the early stages of drug development and the later stages of lead optimization. Pepscan’s conformational protein-protein interaction mapping technology is tailored to cover a wide range of low and high affinity protein-protein interactions. The platform allows the creation of comprehensive libraries comprising of various structural mimics combined with potentially necessary incorporation of non-canonical residues or post-translational modifications mimics. Additionally, substitution analysis pinpoints residues that are essential for a complex to form. This customized approach helps to precisely map proteins’ interaction sites and reveal the fine details of these interactions.
Lead Identification and Validation Services
Drug Discovery & Development Services
Pepscan applies its proprietary peptide technologies, peptide chemistry expertise, immunology know-how and its strong track record in contract research and R&D collaborations for Drug Discovery Services for companies and not-for-profit institutions.
Phage display is a technology that allows the de novo discovery of peptides against any target of interest by exploring DNA-encoded peptide libraries exceeding billions of different members. In this context, we are using our proprietary CLIPS technology to generate highly constrained peptides with enhanced affinity, selectivity and proteolytic stability suited for diagnostic and therapeutic applications. Pepscan’s CLIPS Phage Display highlights: - Phage display platform optimized for identification of CLIPS constrained peptides from high-quality libraries based on trinucleotide technology and diversities exceeding 4E+10 variants. Access to our CLIPS scaffold portfolio containing over 50 different scaffold molecules. World-leading expertise in synthesis of CLIPS-constrained peptides in various formats and scales. Hi-sense peptide array platform for the structural fine-tuning of CLIPS-constrained peptides with a capacity exceeding 100.000 peptides per month. Integration with antibody epitope mapping. Highly trained staff with years of experience in peptide display, synthesis, design, optimization and molecular recognition of peptides. CLIPS-peptide Phage Display Our monocyclic phage display library encodes for 10 random positions (X) flanked by two cysteines (ACXXXXXXXXXXCG). The phage display library was generated with trinucleotides, ensuring an equal distribution of all 19 natural amino acids (excluding Cys) over all randomized positions and possesses a diversity exceeding 4E+10 variants. Pepscan offers a fee for service business model and pricing depends on # of display rounds, specicif target requirements and number of best candidates to further investigate. Typical cost for a project start from 75.000 Euro and turnaround time estimate between 3-4 months.
CLIPS Constrained Peptides
Pepscan is specialized in protein mimicry for the discovery of therapeutics peptides with a drug development program based on its proprietary CLIPS technology. CLIPS peptides have shown benefits in biopharmaceuticals, synthetic immunogens and as high-affinity binders.
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