What Is Liquid Phase Peptide Synthesis?

As the leading peptide manufacturer, Bachem is at the forefront of innovative synthesis methods. One cutting-edge approach is liquid phase peptide synthesis (LPPS), offering numerous advantages over traditional solid phase synthesis for producing peptides and peptide-based therapeutics. Below, we’ll explore what LPPS is, how it works, and its key benefits for accelerating your peptide product development.What exactly is liquid phase peptide synthesis?Liquid-phase peptide synthesis is one of the four main methods for creating peptides.In LPPS, peptides are built step-by-step in solution using soluble tags. These tags, similar to the solid supports in SPPS, simplify the process after each step by making it easier to isolate the product. For this to work, the tags must dissolve in aqueous or organic solvents while remaining distinct from other materials, allowing their removal through methods like precipitation, filtration, or extraction. Choosing the right tags, therefore,  is key to making the process efficient and effective.LPPS is typically used for synthesizing shorter peptides and offers less control over each synthesis step compared to SPPS. While SPPS remains the preferred method for many pharmaceutical applications, LPPS is gaining interest for its scalability and reduced use of reagents and solvents, making it a more sustainable option. What are the benefits of liquid-phase peptide synthesis?LPPS offers a sustainable and scalable approach to peptide production. It requires fewer reagents and solvents compared to other methods, reducing waste and making it more environmentally friendly.LPPS is particularly well-suited for synthesizing shorter peptides, where it delivers high purity and reliable results. Its solution-phase environment supports precise chemical reactions, allowing for efficient peptide bond formation. This can lead to improved yields and cost savings, especially in applications requiring custom peptide sequences.Additionally, LPPS minimises the accumulation of byproducts, simplifying purification and reducing the need for expensive chromatographic methods. These benefits make LPPS an attractive choice for research and therapeutic applications where cost-efficiency, sustainability, and scalability are priorities. What are the differences between liquid phase peptide synthesis and solid-phase peptide synthesis?Liquid phase peptide synthesis and solid-phase peptide synthesis (SPPS) are two primary methods for creating peptides, each with distinct differences. LPPS synthesises peptides in solution, using soluble tags to aid in the separation of peptides from reagents and byproducts. This method is cost-effective, scalable, and more environmentally friendly, making it ideal for shorter peptides. However, LPPS can encounter difficulties with longer peptides due to challenges in maintaining consistent reactions and removing unwanted byproducts.SPPS, on the other hand, attaches the growing peptide chain to a solid resin support, enabling easy removal of excess reagents and byproducts. It’s fast and efficient, particularly for high-throughput synthesis and shorter peptides, and is the go-to method for large-scale production. However, SPPS involves significant use of hazardous reagents and solvents, and struggles with longer or more complex peptides due to limitations in reaction efficiency on the solid support.  What is the method of liquid phase peptides synthesis?LPPS involves building peptides step-by-step in a liquid solution. Here’s a detailed look at the process:Activation: The first amino acid is activated by attaching a special chemical group to make it more reactive. This activation is usually achieved by forming an ester or an anhydride with a coupling reagent.Coupling: The activated amino acid is then combined with another amino acid to form a peptide bond. This step is repeated sequentially, adding one amino acid at a time to extend the peptide chain.Protection and deprotection: To prevent unwanted side reactions, the reactive groups of amino acids (such as the amine group of the next amino acid to be added) are protected by chemical groups. After each coupling step, these protective groups are removed (deprotection) to allow the next amino acid to be added.Purification: After the peptide chain is fully assembled, the mixture is purified to remove by-products and incomplete peptides. This purification is often done using high-performance liquid chromatography (HPLC), which separates the desired peptide from impurities based on differences in their chemical properties.Final deprotection: The final step involves removing any remaining protective groups to obtain the finished peptide in its active form. Why choose our peptide synthesis services?Bachem has 50 years of leadership in taking peptide breakthroughs from discovery to commercialisation. We offer comprehensive services including research and GMP-grade materials, process development, and analytical support across all clinical phases. Our innovative technologies include Molecular Hiving synthesis, continuous chromatography, and eco-conscious manufacturing processes. We also have expertise in modified and augmented peptides with unnatural amino acids, PEGylation, lipidation, glycosylation, imaging agents, and more. As an internationally approved CDMO, our GMP-compliant facilities undergo routine inspections by the FDA, Swissmedic, and other major regulators. Above all, we prioritise excellence through quality, cutting-edge expertise, a focus on sustainability and ethical business practices, and an unwavering commitment to our customers’ success. Contact us today to leverage our exceptional leadership, innovative technologies, comprehensive services, and commitment to quality and expertise.Subscribe to our general newsletter/* "function"==typeof InitializeEditor,callIfLoaded:function(o){return!(!gform.domLoaded||!gform.scriptsLoaded||!gform.themeScriptsLoaded&&!gform.isFormEditor()||(gform.isFormEditor()&&console.warn("The use of gform.initializeOnLoaded() is deprecated in the form editor context and will be removed in Gravity Forms 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