Liquid-phase Peptide Synthesis Services

In the field of medicinal chemistry, peptides consisting of 2 to 50 amino acids are larger than traditional small molecules and smaller than typical biological therapeutics. In addition, peptides are usually produced by chemical synthesis, and their structures can be fine-tuned to be readily diversified. Solid phase synthesis is widely regarded as the gold standard for peptide synthesis. However, liquid phase peptide synthesis could potentially accomplish higher purity, lower reagent consumption, and greater ease of scaling than solid phase method.

Based on the advanced liquid-phase peptide synthesis platform, Amerigo Scientific offers high-purity peptides for your applications requiring exceptional sensitivity. Get an instant quote by filling out the form, or order online to speed up your project.

What is Liquid-phase Peptide Synthesis

Liquid-phase peptide synthesis (LPPS) is another chemical method for peptide synthesis in addition to the traditional solution-phase and solid-phase peptide synthesis (SPPS) methods. LPPS is a strategy that combines the advantages of traditional solution-phase synthesis and solid-phase synthesis, aiming to solve the challenge of tedious purification of intermediates in traditional solution-phase synthesis, while retaining the advantage of homogeneous reactions.

In LPPS, soluble tags are used, which act similarly to the polystyrene-based solid supports used in SPPS, to simplify each step of synthesis. In liquid phase synthesis, the C-terminal amino acid or initiation peptide fragment is covalently linked to a soluble tag with specific physicochemical properties. The tags remain attached to the peptide chain throughout the elongation process. After each coupling and deprotection reaction, the purification step can be simplified by taking advantage of special properties (such as the solubility or size) of the tag to separate the target peptide product from the unreacted starting material, excess reagents, and by-products. Once the peptide chain is fully synthesized, the tag is cleaved from the target peptide.

Soluble tags is a key factor for a successful optimal LPPS strategy. Soluble tags should be easily soluble in aqueous or organic solvents and have properties significantly different from other reagents and by-products so that they can be removed by precipitation, filtration, or extraction at the end of each step.

The scalability of the LPPS method and its potential to reduce the use of reagents and solvents make it more sustainable and environmentally friendly than any other chemical synthesis methods. LPPS is most suitable for the synthesis of short peptides (up to 20 amino acids) for purity sensitive applications.

Advantages of Liquid-phase Peptide Synthesis

Although SPPS is often the first choice for peptide synthesis, enabling low-cost peptide preparation in short turnaround times, the large excess of harmful reagents and solvents required at each step of the SPPS process remains a challenge that needs to be addressed. LPPS has the advantages of the scalability and simplicity of SPPS, as well as the sustainability of traditional solution phase techniques. Alternatively, LPPS is more cost-effective than solution phase synthesis because it uses soluble tags to simplify the purification step in each synthesis cycle.

• Simplified Purification of Intermediates: The separation of the tagged peptide product from unreacted starting materials, excess reagents, and byproducts can be achieved easily, after each coupling and deprotection step.
• Reaction Monitoring and Control: All reactions occur in a homogeneous solution, real-time monitoring of reaction progress and product purity is straightforward using standard analytical techniques, such as mass spectrometry, HPLC, and NMR.
• High Purity of Final Product: The effective purification of intermediates at each step significantly contributes to a higher purity of the final peptide product, reducing the burden on final purification.
• Green Chemistry Principles: The simplified purification steps in LSSP can lead to reduced solvent consumption and waste generation. In addition, the homogeneous nature of the reactions allows for more efficient use of reagents.

Soluble Tags in Liquid-Phase Peptide Synthesis

The development of soluble tags for the liquid-phase synthesis of peptides is a dynamic and active field of research. Ideal tags should differ significantly from reagents and byproducts to streamline purification, and they should also be cost-effective in terms of production and easy to cleave from the final product.

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