Synthetic Peptides as Vaccine Candidates: The Safe, Stable and Efficient Solution

Vaccines have grown to be one of the most successful biomedical advances to prevent life-threatening diseases. Whereas traditional vaccines have proven their efficiency over decades, the development of synthetic peptides as vaccine candidates marks a considerable milestone in the field of vaccinology. 

This approach offers enhanced safety, more stability, and is really efficient in combat against infectious diseases. But what’s so special about synthetic peptides? Let’s take a closer look into the science to understand the important role these small protein fragments play in advancing vaccine development.

Synthetic Peptides: What Are They?

Synthetic peptide vaccines are artificially engineered small chains of amino acids that mimic certain protein regions of viruses, bacteria, or other pathogens. The peptides produced in the laboratory are very similar to the components of the pathogen that are responsible for triggering immune response. 

Therefore, when they are isolated and multiplied, such an immunological effect can be induced without having to resort to the use of the whole organism like traditional vaccination approaches where attenuated or inactivated ones are used. Vaccination by synthetic peptides as vaccines has been found to less likely induce allergic or autoimmune responses due to the lack of redundant elements. (1)

Why Synthetic Peptide Changes the Face of Vaccinology?

Recent advances in the molecular design of synthetic vaccines | Nature Chemistry

Synthetic peptides have certain advantages over traditional vaccine methodologies: 

  1. Improved Safety

The active ingredients in conventional vaccines are usually either live attenuated or inactivated pathogens and therefore pose a lot of risk for people with suppressed immunity causing autoimmune or strong allergic responses. Synthetic peptides as drugs do not carry such risks because they employ just a few harmless fragments of the pathogen. This ensures an effective immune response without harmful side effects, common to vaccines that use whole organisms. (1,2)

  1. Stability and Storage Benefits

Most of the current vaccines are usually temperature-sensitive, especially in areas that lack constant refrigeration. Synthetic peptides are very stable, even at fluctuating temperatures, thus allowing for easier transportation and storage. This attribute will be highly important in international vaccination efforts against diseases in resource-poor countries. (3)

  1. Personalized Medical Treatment

With medicine, however, a one-size-fits-all approach often falls short. Synthetic peptides, therefore, offer great flexibility in the possibility of including diverse chemical modifications, such as non-canonical amino acids or alterations to the peptide backbone. Such modifications may be customized for enhanced stability against proteases and general vaccine efficacy but also to fit the special requirements of each patient, making them ideal for synthetic peptide drugs. (4)

  1. Cost-Efficient 

Such a development in solid phase peptide synthesis (SPPS), with the characteristic automated synthesizers and microwave-assisted techniques, reduced the gap to simplicity, reproducibility, speed, and cost-reduction of peptide production immensely. (1)

This clearly outclasses traditional methods of vaccine production, as synthetic peptide synthesis eliminates the need for culture on a large scale of living organisms, known to be time-consuming and resource intensive.

Scalable Peptide Synthesis for Rapid Global Health Solutions

Efficient and scalable synthesis peptides become even more critical during outbreaks and pandemics, where quick response and resource management are important. 

Further improving the cost efficiency of this technology is Numaferm with its innovative Numaswitch® technology, streamlining the manufacturing process for peptides and proteins and hence further reducing costs of production. (5,6)

Such breakthrough technology can achieve faster, more economical synthesis of peptides and further reinforces its role as a critical solution in large-scale vaccine development and rapid deployment during any global health emergency.

Synthetic Peptides in Action: Present and Future Applications

Three Inventive Biomedical Applications for Synthetic Peptides

Synthetic peptides FDA approval processes currently represent a medical revolution in infectious diseases, cancer immunotherapy, and responses against emerging pathogens. Regarding infectious disease control, clinical trials on HIV, malaria, and influenza use peptides targeting conserved regions of the pathogen to provide broad and durable protection. (7–9)

In cancer immunotherapy, synthetic peptides derived from tumor-specific antigens induce specific immune responses capable of destroying cancer cells with precision and personalization. (10)

In outbreak situations, like COVID-19, synthetic antimicrobial peptides allow the design and deployment of vaccines at incredible velocity—their value is the rapidity and effectiveness of intervention. With their precision, adaptability, and scalability, synthetic peptides are shaping the future of vaccines and therapeutics. (1,4)

Challenges To Overcome

While synthetic peptide vaccines hold great promise, there are many challenges to be overcome in terms of becoming broadly effective. Peptides are generally poor immunogens and mostly require adjuvants or advanced delivery systems in order to improve their immune-stimulating capacity. They are also very susceptible to enzymatic degradation, which limits stability and the shelf life of these peptides. (1)

Furthermore, MHC restriction, variability in immune responses, and the potential for immune tolerance or autoimmunity add complexity to their development. (1,11) These will have to be prevailed before the full potential of synthetic peptide vaccines can be realized.

Conclusion

Synthetic peptides represent a transformative advancement in vaccinology, offering unequaled safety, stability, and adaptability compared to traditional approaches. Their ability to precisely target pathogens, coupled with cost-effective and scalable production methods, makes them a critical tool in addressing both infectious diseases and emerging global health challenges. 

While hurdles such as weak immunogenicity, enzymatic instability, and MHC variability remain, ongoing innovations in adjuvant technologies, delivery systems, and manufacturing processes—like the Numaswitch® technology—are paving the way for their broader application. With continued research and development, synthetic peptides have the potential to revolutionize vaccine development, providing personalized, efficient, and accessible solutions for future healthcare needs.

References

  1. Skwarczynski M, Toth I. Peptide-based synthetic vaccines. Chem Sci. 2015;7(2):842. doi:10.1039/C5SC03892H
  2. Hos BJ, Tondini E, van Kasteren SI, Ossendorp F. Approaches to improve chemically defined synthetic peptide vaccines. Front Immunol. 2018;9(APR):366919. doi:10.3389/FIMMU.2018.00884/BIBTEX
  3. Ashkani EG, McKenna BD, Bryant JL, et al. Stability of Multi-Peptide Vaccines in Conditions Enabling Accessibility in Limited Resource Settings. Int J Pept Res Ther. 2024;30(4):1-6. doi:10.1007/S10989-024-10620-Y/TABLES/2
  4. Groß A, Hashimoto C, Sticht H, Eichler J. Synthetic Peptides as Protein Mimics. Front Bioeng Biotechnol. 2016;3(JAN):211. doi:10.3389/FBIOE.2015.00211
  5. Nguyen BN, Tieves F, Neusius FG, Götzke H, Schmitt L, Schwarz C. Numaswitch, a biochemical platform for the efficient production of disulfide-rich pepteins. Frontiers in Drug Discovery. 2023;3:1082058. doi:10.3389/FDDSV.2023.1082058
  6. Nguyen BN, Tieves F, Rohr T, et al. Numaswitch: an efficient high-titer expression platform to produce peptides and small proteins. AMB Express. 2021;11(1). doi:10.1186/s13568-021-01204-w
  7. Wang TT, Tan GS, Hai R, et al. Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes. Proceedings of the National Academy of Sciences. 2010;107(44):18979-18984. doi:10.1073/PNAS.1013387107
  8. Wang CY, Shen M, Tam G, et al. Synthetic AIDS vaccine by targeting HIV receptor. Vaccine. 2002;21(1-2):89-97. doi:10.1016/S0264-410X(02)00432-2
  9. Corradin G, Céspedes N, Verdini A, Kajava A V., Arévalo-Herrera M, Herrera S. Malaria vaccine development using synthetic peptides as a technical platform. Adv Immunol. 2012;114:107-149. doi:10.1016/B978-0-12-396548-6.00005-6
  10. Stephens AJ, Burgess-Brown NA, Jiang S. Beyond Just Peptide Antigens: The Complex World of Peptide-Based Cancer Vaccines. Front Immunol. 2021;12:696791. doi:10.3389/FIMMU.2021.696791
  11. Naeimi R, Bahmani A, Afshar S. Investigating the role of peptides in effective therapies against cancer. Cancer Cell Int. 2022;22(1). doi:10.1186/S12935-022-02553-7

Latest Trends in Biotherapeutics: Focus on Protein Drugs

Biotherapeutics and advanced therapies | Protein Drugs

Biotherapeutics are transforming the health care landscape through new ways of treating diseases that were previously complex in severity, thus improving outcomes in patients. Protein drugs represent one of the major research and development areas in the field of biotherapeutics, owing to their wide applications in the targeted therapies of hard-to-treat diseases.

Evolution of Protein Drugs in Biotherapeutics

Biotherapeutics, also referred to as biologics, are drugs that are produced from living organisms or their cells. Protein drugs, as a key subclass of therapeutic proteins​, are designed to interact specifically with biological pathways in the body.. (5)

Insulin, discovered almost a century ago, was the advent of protein drugs and one of the most important events in the history of medicine. (1) Today, it includes monoclonal antibodies (mAbs), cytokines, fusion proteins, among others, with gigantic expansion into the scope and variety of protein therapeutics. (2)

Today, protein drugs are a cornerstone of protein therapy, revolutionizing treatments for cancer, autoimmune diseases, and genetic disorders by acting only on disease-specific molecules, hence reducing side effects and opening the doors to personalized medicine. Specificity, potency, and versatility have allowed these drugs to gain a foothold within the wider therapeutic arsenal and to offer new hopes to patients with conditions that were previously difficult to treat. (3-5)

The Expanding Use of Protein-Based Drugs 

The therapeutic effect of protein-based drugs is created by selective interaction with cellular targets modulating biological processes. This makes them useful in treating chronic inflammatory and autoimmune diseases. (5) Consequently, proteins also tend to be highly specific, with reduced activity against off-targets, compared to small-molecule drugs. These complex natures of the three-dimensional structure confer higher-order functions, including receptor blocking and immune modulation-important in the treatment of diseases such as cancer and autoimmune disorders. The promising land for such medications toward personalized therapy comprises the growing demand for biotherapeutics in a number of therapeutic fields, including oncology, immunology, and endocrinology. (5, 6) Fast growth in the pharmaceutical industry and the contributions of leading biotherapeutics companies place protein drugs as pivotal solutions for addressing unmet medical needs. (4)

Protein Therapeutics: Key Types and Functions

Protein drugs are very heterogeneous therapeutic products because of the diverse actions and applications. Below are some of the most common in this dynamic field:

  • Monoclonal Antibodies (mAbs): A major class of recent new medicines approved in the pharmaceutical marketplace is therapeutic monoclonal antibodies. Monoclonal antibodies (mAbs) are among the most well-recognized protein based drugs examples, targeting selected antigens on cancer cells, bacteria, or viruses, with their mode of action being inhibition of cell growth, signaling immune cells to destroy marked cells, or delivery of cytotoxic agents to tumor sites. Since they originate from a clone of one single lymphocyte cell, mAbs represent some of the most powerful tools in targeted therapy at present. (4)
  • Enzymes as therapeutic agents: Enzymes are responsible for catalyzing a wide range of biochemical reactions within the human body. In replacement therapies, particular enzymes might serve in lieu of those lacking or absent to help correct metabolic imbalances in patients and give symptomatic relief. (4)
  • Cytokines, Growth Factors, and Hormones: Cytokines and growth factors are a class of regulatory proteins that are very important in immune responses and cell growth. Depending on their function, therapeutic proteins can either stimulate or dampen the immune function by harnessing these molecules for different functions, acting in critical roles in cancer immunotherapy and tissue repair. (4)
  • Fusion Proteins: A protein combining more than one functional domain into a single therapeutic protein is called a fusion protein. Such proteins show increased therapeutic effect due to concurrent binding to various cell types or pathways, and such proteins are desirable in diseases like cancer and autoimmune diseases. Fusion proteins generally show dual action which increases their potency as well as scope beyond conventional treatment. (2)
  • Peptide Therapeutics: Peptides are short chains of amino acids that have proven to be of considerable value as therapeutic agents. They can mimic many of the biological activities of proteins but enjoy better safety profile and enhanced bioavailability. Yet, the latter characteristic presents an Achilles heel because their small sizes make peptides more susceptible to degradation. Although these factors present major formulation and delivery hurdles, their high specificity and generally low toxicity continues to fuel interest in this class of drugs. (3,7)

Protein Drug Development Challenges 

Protein drugs are changing the face of treatment in many areas, since they have specific advantages over conventional small-molecule drugs. Due to their highly target-specific natures, FDA approved protein drugs offer minimal off-target effects, hence limited side effects and a particularly appropriate feasibility for long-term administration. (5) Their reduced toxicity is highly important in areas such as oncology, where protecting healthy cells is critical; the biocompatibility-with structures similar to natural proteins-means there are fewer side effects, and the body can process it without major risks of refusal or serious immune response. (8)

On the other hand, protein drugs face a different set of challenges. Due to their inherent tendency to aggregate, degrade, or denature, proteins usually have short half-lives, which often equate to short half times and frequent dosing or special formulations. Immunogenicity is another challenge, although researchers are working on structural modifications in efforts to improve tolerance. Common approaches being used include PEGylation, glycosylation, lipidation, and protein fusion, all with the goal of increasing stability and reducing immune responses. (5)

Production of therapeutic proteins is also not straightforward. Many protein therapeutics, including mAbs and fusion proteins, may be over 100 kDa, making the chemical synthesis technically difficult. They are to be produced in living cells, which indicates that factors like cell line option, species origin, and conditions of cultivation highly influence the features of the final product. Such complex characteristics in various proteins make many of the recombinant production strategies inefficiently yield poor products or generate purified products which have no functionality due to non-conserved conformations. (5)

Numaswitch® – Peptide and Protein Production Made Easy

In order to meet the challenges presented by the production of these molecules, Numaferm developed Numaswitch®, a platform technology for high-efficiency, large-scale production of peptide and protein therapeutics. Central to this technology is a reagent called the Switchtag, a bivalent protein tag. Fusion with a protein of interest yields a fusion protein that forms aggregates in E. coli cells; this acts to protect the target protein against proteolytic degradation. As observed, Switchtags are refolding tags that, upon extraction, ensure correct refolding of target proteins with a calcium ion and hence preserve the secondary and tertiary structures of proteins required for protein function. Employment of such technology has greatly simplified the production of high-quality protein drugs for a number of therapeutic applications. (9,10)

Conclusion

The bio-therapeutic horizon is, therefore, rapidly evolving where protein-based drugs have emerged as the new game changers for the treatment of several complex diseases. With further advances in protein engineering and recombinant DNA technology, these therapeutics offer solutions tailored to the required needs with improved efficacy and fewer side effects. Research is still continuing despite all the challenges associated with production and stability, and new technologies such as Numaswitch® point to better manufacturing processes. The future of biotherapeutics looks great, and protein drugs have been expanding this therapeutic armory and bring new hope to the previously hopeless patient.

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References

  1. Vecchio I, Tornali C, Bragazzi NL, Martini M. The discovery of insulin: An important milestone in the history of medicine. Front Endocrinol (Lausanne). 2018;9:343536. doi:10.3389/FENDO.2018.00613/BIBTEX
  2. Lee SJ, Chinen J, Kavanaugh A. Immunomodulator therapy: Monoclonal antibodies, fusion proteins, cytokines, and immunoglobulins. Journal of Allergy and Clinical Immunology. 2010;125(2 SUPPL. 2):S314-S323. doi:10.1016/J.JACI.2009.08.018/ASSET/12FE8CCB-DF0A-4494-A7E4-7C8F060771DB/MAIN.ASSETS/GR1.JPG
  3. Halawa M, Akantibila M, Reid BE, Carabetta VJ. Therapeutic proteins have the potential to become new weapons in the fight against antibiotic resistance. Frontiers in Bacteriology. 2023;2:1304444. doi:10.3389/FBRIO.2023.1304444
  4. Sauna ZE, Lagassé HAD, Alexaki A, et al. Recent advances in (therapeutic protein) drug development. F1000Res. 2017;6:113. doi:10.12688/F1000RESEARCH.9970.1
  5. Ebrahimi SB, Samanta D. Engineering protein-based therapeutics through structural and chemical design. Nat Commun. 2023;14(1):1-11. doi:10.1038/S41467-023-38039-X
  6. Jung SM, Kim WU. Targeted Immunotherapy for Autoimmune Disease. Immune Netw. 2022;22(1):e9. doi:10.4110/IN.2022.22.E9
  7. Wang L, Wang N, Zhang W, et al. Therapeutic peptides: current applications and future directions. Signal Transduct Target Ther. 2022;7(1). doi:10.1038/s41392-022-00904-4
  8. Zaman R, Islam RA, Chowdhury EH. Evolving therapeutic proteins to precisely kill cancer cells. J Control Release. 2022;351:779-804. doi:10.1016/J.JCONREL.2022.09.066
  9. Nguyen BN, Tieves F, Neusius FG, Götzke H, Schmitt L, Schwarz C. Numaswitch, a biochemical platform for the efficient production of disulfide-rich pepteins. Frontiers in Drug Discovery. 2023;3:1082058. doi:10.3389/FDDSV.2023.1082058
  10. Nguyen BN, Tieves F, Rohr T, et al. Numaswitch: an efficient high-titer expression platform to produce peptides and small proteins. AMB Express. 2021;11(1). doi:10.1186/s13568-021-01204-w

Antimicrobial Peptides Lead The Future of Antibiotic Solutions

Synergistic action of antimicrobial peptides and antibiotics: current understanding and future directions
antimicrobial peptides

Antibiotics have been used to combat bacterial infections for many decades now ever since penicillin was first discovered in 1928 (1). However, a major challenge we are currently facing is the increase of multi-drug resistance in bacteria. Consequently, even the most effective drugs are rendered ineffective and formerly easily treatable infections become much more difficult to cure (2).

This growing threat, in turn, has driven researchers to look beyond conventional antibiotics in the quest to find new, innovative solutions. Among the most promising therapeutic agents in this search are antimicrobial peptides (AMPs). These naturally occurring molecules may hold the key to combat multidrug-resistant pathogens and lead us through the next stages of infection control.

What Are AMPs and How Do They Fight Infections?

AMPs are naturally occurring host defense peptides that take part in the innate immune defense of animals, plants, and even humans, making them a prominent class of antimicrobial proteins. Structurally, AMPs are usually short chains of amino acids, fewer than 50, and exhibit a broad spectrum of activity, positioning them as antimicrobial peptide agents effective against various pathogens, including bacteria, fungi, and viruses. (3)

While conventional antibiotics often target bacterial cellular processes, such as protein synthesis or cell wall formation, antibacterial peptide agents like AMPs primarily attack the microbial cell wall, leading to membrane disruption and cell death. This antibacterial mechanism of action is highly effective not only against common Gram-positive and Gram-negative bacteria but also against antibiotic-resistant strains. (3) Moreover, their ability to destroy biofilm-forming bacterial communities – especially challenging to treat with conventional antibiotics – makes them a valuable prospect for future antibiotic solution. (5,6)

Why Are Antimicrobial Peptides So Important in the Fight Against Antibiotic Resistance?

Antibiotic resistance has escalated into a global health crisis. The overuse and misuse of antibiotics in human medicine and animal husbandry have increased the rate at which multidrug-resistant bacteria spread. Conventional antibiotics cannot be used to kill these strains and infections caused by Methicillin-resistant Staphylococcus aureus and multi-drug-resistant Escherichia coli are increasingly occurring. Doctors are running out of effective methods to treat such infections (2,7).

Here is where peptide antimicrobial agents come into play: because they target the bacterial membrane, an integral part of bacterial structure, it is much harder for bacteria to develop resistance against them. Even in cases when mutations occur, fast and multi-targeted attacks of AMPs make them hard to adapt. This contrasts with conventional antibiotics, which often become ineffective after only a few years of widespread use as bacteria develop resistance to their active ingredients (6).

Applications and Market Opportunities of AMPs and Their Challenges 

Antimicrobial peptides represent a very heterogeneous group, and their benefits extend way beyond fighting resistant bacteria. They exert effects in wound healing by reducing inflammation and the risk of infection (8), have the potential for selective action against cancer cells (9), exhibit activity against viruses like HIV and influenza (10,11), and can be used in food preservation to prolong expiration dates by reducing bacterial load. (12)

Despite such big promises, the translation of anti microbial peptides from laboratory to pharmacy shelves is still problematic. One of the major pitfalls for AMPs is the toxicity: mechanism and action targeting bacterial cells result in the unintended killing of human cells which depends on its dose and can lead to cytotoxic effects in larger quantities. Furthermore, stability problems in the human body have been reported with many AMPs. They are susceptible to enzyme degradation in the body which simultaneously diminishes their efficiency. (3)

AMPs: Challenges in Production and Innovative Solutions 

Although AMPs are relatively short, the biological activity of most of them highly depends on their three-dimensional conformation. Considering the specific structures and folding for such peptides, the production of AMPs by chemical synthesis may be quite challenging. (3) Any structural deviations in the course of production may render these peptides ineffective. Moreover, hazardous chemicals are frequently used for large-scale peptide production, with considerable generation of chemical waste, hence rendering such methods less attractive for wider applications. (13)

The other approach is the use of recombinant technology, where microbes are genetically engineered to produce AMPs. It also has its own setbacks, as the inherent toxicity of AMPs can lead to the death of host cells, thereby giving reduced yields of the products. Besides, the process of isolation and purification of these peptides from the cells usually involves processes that are very resource-intensive and not effective due to aggregating ondr degradation-prone nature for most of the AMPs. (3,14)

To answer these challenges, Numaferm has developed the Numaswitch® platform. This new approach utilizes Switchtags, which are basically protein tags devised to allow efficient expression of AMPs in E. coli in their inactive forms to avoid toxicity. Secondly, Switchtags induce the correct refolding of the peptides in the extracellular medium, which ensures that the peptides become functionally active again. In addition to process scalability, this platform offers a cost-effective and sustainable approach for peptide (and protein) production. (15,16)

The Future of Antimicrobial Peptides

Regardless of the challenges, the prospects for AMP are encouraging. Antibiotic resistance is on the rise, and novel alternative therapeutics and methods of treatments are necessary to treat these infections. The diversity of AMPs, together with their distinctive ability to act against resistant bacteria, puts them as a potential game-changer in contemporary medicine. Several pharmaceutical companies and research organizations have already begun aggressively investing in the development of AMPs, and a few peptides have entered clinical trials already. (17)

Conclusion

AMPs represent a very effective, natural solution to one of the most serious contemporary problems in healthcare: resistance to antibiotics. The unique mechanism of antibacterial action in targeting and destroying bacteria makes it nearly impossible for resistance to develop, giving AMPs an edge over traditional antibiotics. Though there are still challenges ahead, the potential that AMPs hold in leading the future of antibiotic solutions cannot be disputed.

With this in mind, Numaferm engineered the Numaswitch® platform to address large-scale production problems of these therapeutic agents in a very specific way. Switchtags induce the production of AMPs in their inactive forms in E. coli and enable proper refolding in the extracellular medium in a second step. Toxicity problems of host cells are thus circumvented and contribute to the establishment of scalable and cost-efficient processes for AMP production. This represents progress that could very well be the cornerstone of infection management in a world where antibiotics are simply no longer enough.

Curious about more info on antimicrobial peptides? Continue to monitor our blog for news about recent biotech inventions!

References

  1. Alexander Fleming Discovery and Development of Penicillin – Landmark – American Chemical Society. Accessed October 23, 2024. https://www.acs.org/education/whatischemistry/landmarks/flemingpenicillin.html
  2. Llor C, Bjerrum L. Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem. Ther Adv Drug Saf. 2014;5(6):229. doi:10.1177/2042098614554919
  3. Huan Y, Kong Q, Mou H, Yi H. Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields. Front Microbiol. 2020;11:582779. doi:10.3389/FMICB.2020.582779/BIBTEX
  4. Savitskaya A, Masso-Silva J, Haddaoui I, Enany S. Exploring the arsenal of antimicrobial peptides: Mechanisms, diversity, and applications. Biochimie. 2023;214:216-227. doi:10.1016/J.BIOCHI.2023.07.016
  5. Yasir M, Willcox MDP, Dutta D. Action of Antimicrobial Peptides against Bacterial Biofilms. Materials. 2018;11(12):2468. doi:10.3390/MA11122468
  6. Rima M, Rima M, Fajloun Z, Sabatier JM, Bechinger B, Naas T. Antimicrobial Peptides: A Potent Alternative to Antibiotics. Antibiotics 2021, Vol 10, Page 1095. 2021;10(9):1095. doi:10.3390/ANTIBIOTICS10091095
  7. Harkins CP, Pichon B, Doumith M, et al. Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice. Genome Biol. 2017;18(1):1-11. doi:10.1186/S13059-017-1252-9/FIGURES/4
  8. Thapa RK, Diep DB, Tønnesen HH. Topical antimicrobial peptide formulations for wound healing: Current developments and future prospects. Acta Biomater. 2020;103:52-67. doi:10.1016/J.ACTBIO.2019.12.025
  9. Tornesello AL, Borrelli A, Buonaguro L, Buonaguro FM, Tornesello ML. Antimicrobial Peptides as Anticancer Agents: Functional Properties and Biological Activities. Molecules. 2020;25(12):2850. doi:10.3390/MOLECULES25122850
  10. Hsieh IN, Hartshorn KL. The Role of Antimicrobial Peptides in Influenza Virus Infection and Their Potential as Antiviral and Immunomodulatory Therapy. Pharmaceuticals. 2016;9(3):53. doi:10.3390/PH9030053
  11. Wang G. Natural antimicrobial peptides as promising anti-HIV candidates. Curr Top Pept Protein Res. 2012;13:93. Accessed October 23, 2024. https://pmc.ncbi.nlm.nih.gov/articles/PMC4730921/
  12. Liu Y, Sameen DE, Ahmed S, Dai J, Qin W. Antimicrobial peptides and their application in food packaging. Trends Food Sci Technol. 2021;112:471-483. doi:10.1016/J.TIFS.2021.04.019
  13. Isidro-Llobet A, Kenworthy MN, Mukherjee S, et al. Sustainability Challenges in Peptide Synthesis and Purification: From R&D to Production. Journal of Organic Chemistry. 2019;84(8):4615-4628. doi:10.1021/acs.joc.8b03001
  14. Yu H, Li H, Gao D, Gao C, Qi Q. Secretory production of antimicrobial peptides in Escherichia coli using the catalytic domain of a cellulase as fusion partner. J Biotechnol. 2015;214:77-82. doi:10.1016/J.JBIOTEC.2015.09.012
  15. Nguyen BN, Thieves F, Rohr T, et al. Numaswitch: an efficient high-titer expression platform to produce peptides and small proteins. AMB Express. 2021;11(1). doi:10.1186/s13568-021-01204-w
  16. Nguyen BN, Thieves F, Neusius FG, Götzke H, Schmitt L, Schwarz C. Numaswitch, a biochemical platform for the efficient production of disulfide-rich proteins. Frontiers in Drug Discovery. 2023;3:1082058. doi:10.3389/FDDSV.2023.1082058
  17. Cresti L, Cappello G, Pini A. Antimicrobial Peptides towards Clinical Application—A Long History to Be Concluded. International Journal of Molecular Sciences 2024, Vol 25, Page 4870. 2024;25(9):4870. doi:10.3390/IJMS25094870

Peptide Synthesis Methods for Drug Development: The Future of Therapeutics

peptide synthesis methods

In recent years, peptide-based drugs have emerged as a groundbreaking approach in modern medicine. With their ability to treat a wide array of conditions—from cancer to autoimmune disorders—peptides are gaining significant attention. (1,10) However, one key challenge remains: efficiently producing peptides at scale for therapeutic use. This is where advanced peptide synthesis methods come into play, and innovative technologies like Numaswitch® evolved by the biotechnology company Numaferm are changing the game in peptide development. (7,8)

In this blog, we’ll explore the most common peptide synthesis methods and introduce how Numaswitch® is setting new standards in the field of drug development.

 

What Are Peptides and Why Are They Important?

Peptides are short chains of amino acids that play crucial roles in biological processes, making them vital in what is peptide synthesis for drug development. They act as messengers, hormones, and growth factors, making them valuable in drug development. Unlike traditional drugs, peptides can target specific cell surface receptors and trigger intracellular pathways with precision, reducing unwanted side effects and improving efficacy. As a result, peptide therapeutics are increasingly being developed for diseases such as cancer, diabetes, and metabolic disorders. (11)

However, the process of synthesizing peptides—especially in large quantities—poses a significant challenge. (3,4) Drug developers need efficient and scalable methods to meet the growing demand for peptide-based treatments.

 

Traditional Peptide Synthesis Methods

There are two main methods used to synthesize peptides: Solid-Phase Peptide Synthesis (SPPS) and Liquid-Phase Peptide Synthesis (LPPS). Let’s break down these methods and their applications.

 

  • Solid-Phase Peptide Synthesis (SPPS)

SPPS is the most widely utilized technique for synthesizing peptides. It involves assembling amino acids one at a time on a solid resin support. The method is highly efficient for short peptide sequences and allows for rapid assembly, highlighting the importance of polypeptide synthesis methods in modern biotechnology. It has become the go-to method in labs because of its speed and ease of automation. (6)

 

Advantages of SPPS

  • High speed and efficiency for short peptides.
  • Ideal for laboratory-scale synthesis.
  • Well-suited for peptides under 50 amino acids. 

 

Challenges of SPPS

  • Difficult to scale for longer peptides.
  • High cost of raw materials.
  • Significant chemical waste, leading to environmental concerns.

 

  •  Liquid-Phase Peptide Synthesis (LPPS)

LPPS differs from SPPS in that it assembles peptides in a liquid solution, a key technique in peptide synthesis in solution. It offers more flexibility for producing longer and more complex peptides. While it’s more suitable for large-scale synthesis, LPPS, one of the main polypeptide synthesis methods for drug development and industrial pharmacy, requires longer reaction times and more intensive purification steps. (9)

 

Advantages of LPPS

  • Better suited for longer peptides and complex structures.
  • More scalable than SPPS for industrial production.

 

Challenges of LPPS

  • Slower process and higher labor intensity.
  • Requires extensive purification, which adds cost and complexity.

 

Numaswitch® Technology: A Game-Changer in Peptide Synthesis

As peptide therapeutics become more important, there’s a growing need for a more efficient, scalable, and sustainable way to produce peptides. That’s where Numaferm and their Numaswitch® technology step in to make a difference.

Numaswitch® offers a breakthrough approach to peptide synthesis procedures by using biological fermentation instead of traditional chemical processes. Numaferm has developed a technology where microorganisms act as peptide factories, significantly reducing the cost and environmental impact of production. (7,8)

 

Key Benefits of Numaswitch®

 

1. Scalability

One of the most significant limitations of SPPS and LPPS is the challenge of scaling up for commercial production. (3,4) Numaswitch® excels here, enabling large-scale peptide production using bio-based methods. This is crucial for meeting the growing demand for peptide drugs.

 

2. Cost-Efficiency

Traditional methods like SPPS can be expensive, especially when producing longer peptide chains, but advanced peptide coupling methods can help streamline this process. (2) By using microbial fermentation, Numaswitch® cuts costs while still delivering high-quality peptides, making peptide therapeutics more accessible for pharmaceutical companies.

 

3. Sustainability

With the pharmaceutical industry under increasing pressure to reduce its environmental footprint, Numaswitch® stands out for its eco-friendly process. Unlike SPPS, which generates significant chemical waste. (4,5) Numaswitch® minimizes the use of toxic reagents and solvents, offering a sustainable approach to peptide synthesis mechanisms.

 

4. Versatility and Precision

Whether you’re developing a short peptide sequence or a more complex, longer chain, Numaswitch® is versatile enough to accommodate a wide range of peptide needs, following peptide synthesis methods and protocols pdf. This flexibility makes it an ideal choice for peptide drug development, particularly in personalized medicine.

 

The Future of Peptide Therapeutics with Numaswitch®

As peptide-based drugs continue to reshape the pharmaceutical landscape, the importance of efficient and scalable peptide synthesis approaches cannot be overstated in the field of modern therapeutics. The Numaswitch® technology is paving the way for a new era of peptide production—one that is not only more cost-effective but also more sustainable.

With Numaswitch®, drug developers can produce large quantities of high-quality peptides faster and with less environmental impact, making it easier to bring life-saving treatments to the market. (7,8) From cancer therapies to treatments for chronic diseases, the potential applications for peptide therapeutics are vast, and Numaswitch® is leading the charge.

 

Conclusion

The demand for peptide-based drug delivery system is only going to increase as their effectiveness in treating complex diseases becomes more apparent. But for these therapies to truly transform healthcare, drug developers need efficient, scalable, and sustainable peptide synthesis methods. Numaswitch® meets this demand by offering an innovative solution that reduces costs, scales easily, and minimizes environmental impact.

As peptide therapeutics continue to grow, Numaferm is poised to be a key player in the future of peptide-based drug development. With their Numaswitch® technology, they’re not just making peptide production more efficient—they’re making it smarter and greener.

Interested in the future of peptide-based drugs in medical practice? Subscribe to our newsletter for updates on synthesis, drug development, and biotech innovations!

 

References

  1. Anderton, S. M. (2001). Peptide-based immunotherapy of autoimmunity: A path of puzzles, paradoxes and possibilities. In Immunology (Vol. 104, Issue 4, pp. 367–376). 
  2. Chandrudu, S., Simerska, P., & Toth, I. (2013). Chemical Methods for Peptide and Protein Production. Molecules, 18(4), 4373. 
  3. Haji, M., Somehsaraie, A., Fathi Vavsari, V., Kamangar, M., & Balalaie, S. (2022). Chemical Wastes in the Peptide Synthesis Process and Ways to Reduce Them. Iran J Pharm Res, 21(1), 123879. 
  4. Isidro-Llobet, A., Kenworthy, M. N., Mukherjee, S., Kopach, M. E., Wegner, K., Gallou, F., Smith, A. G., & Roschangar, F. (2019). Sustainability Challenges in Peptide Synthesis and Purification: From R&D to Production. Journal of Organic Chemistry, 84(8), 4615–4628. 
  5. Martin, V., Egelund, P. H. G., Johansson, H., Thordal Le Quement, S., Wojcik, F., & Sejer Pedersen, D. (2020). Greening the synthesis of peptide therapeutics: an industrial perspective. RSC Advances, 10(69), 42457. 
  6. Merrifield, R. B. (1963). Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide. Journal of the American Chemical Society, 85(14), 2149–2154. 
  7. Nguyen, B. N., Tieves, F., Rohr, T., Wobst, H., Schöpf, F. S., Solano, J. D. M., Schneider, J., Stock, J., Uhde, A., Kalthoff, T., Jaeger, K. E., Schmitt, L., & Schwarz, C. (2021). Numaswitch: an efficient high-titer expression platform to produce peptides and small proteins. AMB Express, 11(1). 
  8. Nguyen, B.-N., Tieves, F., Neusius, F. G., Götzke, H., Schmitt, L., & Schwarz, C. (2023). Numaswitch, a biochemical platform for the efficient production of disulfide-rich pepteins. Frontiers in Drug Discovery, 3, 1082058. 
  9. Sharma, A., Kumar, A., de La Torre, B. G., & Albericio, F. (2022). Liquid-Phase Peptide Synthesis (LPPS): A Third Wave for the Preparation of Peptides. Chemical Reviews, 122(16), 13516–13546. 
  10. Vadevoo, S. M. P., Gurung, S., Lee, H. S., Gunassekaran, G. R., Lee, S. M., Yoon, J. W., Lee, Y. K., & Lee, B. (2023). Peptides as multifunctional players in cancer therapy. In Experimental and Molecular Medicine (Vol. 55, Issue 6, pp. 1099–1109). Springer Nature.
  11. Wang, L., Wang, N., Zhang, W., Cheng, X., Yan, Z., Shao, G., Wang, X., Wang, R., & Fu, C. (2022). Therapeutic peptides: current applications and future directions. In Signal Transduction and Targeted Therapy (Vol. 7, Issue 1). Springer Nature.