SPPS technology efficiently synthesizes peptides by stepwise assembly of amino acids on a solid support, making it widely applicable in drug development, research, diagnostics, and more. Creative Peptides offers customized SPPS services, helping clients overcome synthesis challenges, accelerate project progress, and ensure high-purity, high-efficiency peptide synthesis to meet diverse research and commercialization needs.
The core of peptide synthesis involves the formation of a covalent bond between the carboxyl group of one AA and the amino group of another, resulting in the release of H2O. The activation of the carboxyl group with coupling reagents enhances reactivity, facilitating efficient bond formation. Removal of protective groups ensures that subsequent reactions can proceed without interference. In SPPS, two primary tactics are employed: the butyloxycarbonyl (Boc)/Bzl and the 9-fluorenylmethoxycarbonyl (Fmoc)/t-Bu methods for T/Pn protecting groups. The previous method relies on the incremental acid sensitivity of the side-chain protecting groups.
This method involves the removal of the Boc group using either pure trifluoroacetic acid (TFA) or TFA in dichloromethane, while side-chain protecting groups and peptide-resin connections are eliminated at the conclusion of synthesis by treatment with a strong acid, specifically anhydrous hydrofluoric acid (HF). This method facilitates the efficient synthesis of big peptides and tiny proteins; nevertheless, the utilization of extremely hazardous HF and the requirement for specialized polytetrafluoroethylene-lined equipment restrict its application to experts exclusively. Furthermore, the use of very acidic conditions might induce detrimental alterations in the structural integrity of peptides with sensitive sequences.
The Fmoc/t-Bu technique relies on an orthogonal protective group strategy. This method employs the base-labile N-Fmoc group to preserve the α-amino function, alongside acid-labile side-chain protecting groups and acid-labile linkers that form the C-terminal amino acid protective group. This technique has the benefit of utilizing distinct processes to eliminate temporary and permanent orthogonal protections, so permitting the application of gentler acidic conditions for the ultimate deprotection and breaking of the peptide from the resin. Consequently, the Fmoc-based SPPS approach has become the preferred technique for the regular synthesis of peptides.
Fig.1 Solid-phase peptide assembly with Fmoc amino acids1,2.
In SPPS, linear synthesis and convergent synthesis are the two main approaches.
Linear Synthesis: In SPPS, linear synthesis is a traditional method where amino acids are added one at a time in a sequential manner to construct the desired peptide. This approach is efficient for producing peptides with a relatively short length, typically up to around 50 residues. The main limitation of linear synthesis is its difficulty in efficiently synthesizing longer peptides due to issues with coupling efficiency and the increasing complexity of longer chains. Standard coupling reagents and chemo-selective methods are employed to ensure the correct linkage of each amino acid during the synthesis process.
Convergent Synthesis: Convergent synthesis, on the other hand, involves the synthesis of peptide fragments independently on solid support, followed by their assembly into a full-length peptide. This approach is particularly advantageous for synthesizing longer peptides, typically those with more than 50 amino acids. Convergent synthesis allows for the use of chemical ligation methods such as native chemical ligation (NCL), α-ketoacid-hydroxylamine ligation (KAHA), salicylaldehyde (SAL) ester-mediated ligation, and traceless-Staudinger ligation. These methods enable the joining of larger fragments while minimizing the challenges associated with protecting N- or C-terminal fragments and side chains, which are typically required in standard fragment condensation methods. The development of these ligation techniques has significantly expanded the capability to synthesize complex peptides and small proteins with greater precision and efficiency.
Table 1. Solid-Phase Peptide Synthesis Raw Materials Catalog.
| Amino Acids ' Derivatives | Stable Isotope Labeled Amino Acids | Protected Amino Acids |
| Glycosylated Amino Acids | Chelate Peptides (DOTA related peptides) | Cyclic Peptides |
The utilization of solid support in peptide synthesis offers clear advantages due to the multiple repeating procedures involved.
High Purity and Yield: A high concentration of reagents in such a system can effectively push coupling reactions to completion. Excess reagents and byproducts can be isolated from the developing and insoluble peptide using filtration and washing, with all synthesis stages conducted in a single vessel without material transfer.
Rapid Synthesis: The automation of SPPS can markedly accelerate the synthesis process, enabling peptide manufacturing within hours or days. Simultaneous synthesis of several peptides can be achieved with various resin supports, hence enhancing throughput.
Flexible Scale: SPPS can be adjusted in size according to the required peptide quantity, rendering it appropriate for both small-scale research endeavors and large-scale industrial manufacturing.
Customization: SPPS facilitates the integration of diverse changes (e.g., post-translational modifications, cyclization) and non-standard AAs, enabling the engineering of peptides with tailored characteristics. Protective groups can be individually added and deleted, facilitating fine control over the final structure.
SPPS technology demonstrates significant advantages in the large-scale production of active pharmaceutical peptides. Through fully automated synthesis lines, peptides can be synthesized efficiently, and production cycles are significantly shortened. This technology not only improves production efficiency but also provides reliable process support for the industrialization and commercialization of peptide-based drugs.
Targeted modifications of peptide drugs, such as PEGylation or fatty acid modification, introduce specific functional groups through solid-phase carriers, effectively improving the pharmacokinetic properties of the peptides. These modifications can improve the peptide's stability, extend its duration of action, and enhance its overall performance, contributing to more effective peptide drug development.
SPPS technology is widely used in the development of peptide vaccines. By synthesizing specific antigenic peptides, it is possible to trigger a specific immune response in the body. These peptide vaccines can be used for the prevention or treatment of various infectious diseases and cancers, providing an efficient and controllable method for the rapid development and production of vaccines.
PDCs are an innovative class of drugs where peptides are linked to small molecules or toxins, commonly used in targeted therapy. SPPS technology can synthesize peptides with specific functional groups for conjugation with small molecule drugs or toxins, enabling precise targeted therapy and improving the therapeutic efficacy and safety of the drugs.
Creative Peptides leverages state-of-the-art solid-phase peptide synthesis technology to offer comprehensive peptide synthesis solutions for research and commercial applications. With a focus on precision, reliability, and scalability, the company specializes in the custom synthesis of peptides, from small-scale R&D to large-scale commercial production. Their expertise includes synthesizing complex peptides, including those with non-natural amino acids, cyclic peptides, and conjugates. Creative Peptides is committed to maintaining high standards in peptide purity, quality, and overall process efficiency, ensuring that clients receive peptides tailored to their specific needs, whether for drug development, diagnostic applications, or basic research.
Creative Peptides utilizes fully automated solid-phase peptide synthesis platforms to streamline the peptide synthesis process. This automation ensures consistency, reduces human error, and accelerates the production process. Automated SPPS allows for high-throughput synthesis, facilitating the rapid generation of peptide libraries for screening, optimization, and drug discovery. The fully integrated systems enable precise control over reaction conditions and peptide assembly, ensuring high-quality products that meet strict standards for purity and activity. This advanced technology also minimizes costs and turnaround times, making it an ideal solution for both large-scale and high-volume peptide production.
Creative Peptides offers a wide range of peptide modification services to meet diverse research and therapeutic needs. Peptides can be modified with functional groups, such as PEGylation, fatty acids, or bioconjugates, to enhance their pharmacokinetic properties, improve stability, or reduce immunogenicity. In addition to chemical modifications, Creative Peptides provides peptide labeling services, including fluorescent, radioactive, and affinity tags, for applications in diagnostics, imaging, and tracking. The flexibility in modifications allows for the creation of peptides with tailored properties, optimizing their performance in drug development, biomarker discovery, and other applications.
Creative Peptides excels in large-scale solid-phase peptide synthesis, enabling the efficient production of peptides in kilogram quantities. The company's automated synthesis platforms can scale up peptide production from milligram to kilogram quantities while maintaining high yields and purity levels. This capability is crucial for the industrial production of peptide-based therapeutics, including peptide drugs, vaccines, and other biologics. With advanced purification methods and robust quality control systems, Creative Peptides ensures that peptides produced at scale meet stringent standards and are suitable for commercial use. Their large-scale synthesis services are designed to support various production needs, offering a reliable and scalable solution for peptide manufacturing.
Table 2. Custom Peptide Synthesis and Functionalization Services at Creative Peptides.
Creative Peptides' SPPS technology has been successfully applied in various industries, helping clients overcome synthesis challenges and accelerate project progress. Below are several representative client cases showcasing the advantages and outcomes of SPPS in different fields, illustrating how Creative Peptides' expertise has contributed to the success of diverse projects.
SPPS technology has been successfully applied in various industries, helping clients overcome synthesis challenges and accelerate project progress. Below are several representative client cases showcasing the advantages and outcomes of SPPS in different fields.
In a targeted antibody drug development project, we synthesized a phosphorylated peptide for a client, which was used to evaluate the binding efficiency between the receptor and the antibody. The peptide was 15 amino acids long and included a specific phosphorylation site. Using SPPS, we successfully introduced the modification, enabling efficient synthesis. The client noted that the SPPS method not only accelerated the synthesis but also significantly sped up the subsequent antibody screening and validation process. Additionally, SPPS's efficiency helped save time and costs, providing valuable experimental data for further drug development.
In a vaccine research project, we synthesized multiple peptides targeting specific pathogen antigens for a biotechnology company, used in immunogenicity testing. The peptides ranged from 10 to 25 amino acids in length, with some containing disulfide bonds to mimic the natural conformation of the antigen. SPPS enabled the efficient synthesis of these peptides, ensuring structural stability and meeting the client's specifications. This case demonstrated how SPPS can address the need for complex peptide sequences and structural modifications, significantly enhancing vaccine development efficiency.
A company focused on developing early-stage cancer diagnostic tools needed to synthesize various peptides for antibody screening. These peptides, typically 12 to 18 amino acids long, contained point mutations to assess antibody binding to specific antigens. Using SPPS, we provided the client with customized peptides, ensuring batch consistency and high activity. The client reported that SPPS enabled them to obtain the necessary peptides in a short timeframe, greatly accelerating the biomarker screening process and providing crucial support for the development of early cancer detection tools.
Customer feedback is a driving force behind our continuous improvement. Many long-term clients have given us outstanding reviews, praising our professionalism, timely delivery, and high product quality. Below are key points summarizing the positive feedback from our clients:
1. Efficient Service
Clients consistently commend our high efficiency in peptide synthesis, especially for complex projects or urgent requests, where we manage to deliver on time and keep the project on track.
2. Excellent Quality
In the biopharmaceutical sector, clients frequently highlight the excellent quality of our peptides, noting their high purity and stability. Our products consistently meet their research needs and maintain reliability across multiple collaborations.
3. Time and Cost Savings
Many clients appreciate that choosing our SPPS services has saved them both time and costs. The efficient synthesis process enables them to complete research tasks faster and shorten project timelines, resulting in overall cost reductions.
4. Professional Technical Support
Clients highly praise our technical support team, especially for our ability to solve technical challenges and provide expert advice. Our team's responsiveness and professionalism ensure a seamless experience for customers throughout the entire process.
5. Long-Term Stable Partnerships
Several long-term clients have expressed their satisfaction with the stable, trust-based partnerships we've built. They consider us a reliable peptide synthesis partner and look forward to continuing our collaboration for many years.
Starting a project with us using SPPS is straightforward. We offer customized services based on your specific needs. Whether you're new to peptide synthesis or have a defined project requirement, our expert team will guide you through the process, providing detailed support at every stage. From consultation to delivery, we ensure the highest standards of quality and efficiency, allowing you to kickstart and progress your project smoothly and on time.
Our collaboration begins with an initial consultation, where we discuss your specific needs and project goals. Based on your requirements, our team provides a detailed synthesis plan, timeline, and cost estimate. Once the plan is confirmed, we begin peptide synthesis and carry out stringent quality control to ensure the highest product standards. Upon completion, we deliver the peptides on time along with any necessary quality reports, ensuring your satisfaction.
If you have any peptide synthesis needs or questions, feel free to reach out to our team. We offer easy ways to contact us via email, phone, or online inquiry forms. Our experts will provide personalized solutions based on your specific project requirements and offer a detailed quote. Whether you're working on small-scale research or large-scale production, we offer flexible, efficient services tailored to your needs.
Our service goes beyond peptide synthesis and delivery. Throughout your project, you'll receive comprehensive technical support to resolve any issues that may arise during the synthesis process. If you need guidance on peptide applications or encounter any challenges after delivery, our expert team is here to assist you. We also provide robust after-sales services to ensure you have a seamless experience with our products, making sure you receive the necessary assistance whenever you need it.
References
