What is Tag-Assisted Peptide Synthesis (TAPS)?

As the leading peptide manufacturer, Bachem is at the forefront of innovative synthesis methods. One cutting-edge approach is tag-assisted (liquid phase) peptide synthesis (TAPS), offering numerous advantages over traditional solid phase synthesis for producing peptides and peptide-based therapeutics. Below, we’ll explore what TAPS is, how it works, and its key benefits for accelerating your peptide product development.

What exactly is Tag-Assisted Liquid Phase Peptide Synthesis?

Classic liquid-phase peptide synthesis (LPPS) is one of the four main methods for creating peptides. One special case of LPPS is TAPS.

In TAPS, 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 organic solvents while remaining distinct from other materials, allowing their removal through methods like precipitation, filtration, or extraction. Choosing the right tag, therefore, is key to making the process efficient and effective.

In the past, TAPS has typically been used for synthesizing shorter peptides as it offered less control over each synthesis step compared to SPPS. While SPPS remains the preferred method for many pharmaceutical applications, TAPS has been established and better understood as a platform technology in recent years. Growing interest in the approach is driven by its scalability and reduced use of reagents and solvents, making it a more sustainable option.

What are the benefits of Tag-Assisted Liquid Phase Peptide Synthesis?

TAPS offers a sustainable and scalable approach to peptide production. It requires fewer reagents and much less solvents compared to other methods, reducing organic waste and making it more environmentally friendly.

TAPS is particularly well-suited for synthesizing short-to-medium sized 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.

What are the differences between Liquid Phase Peptide Synthesis (LPPS), Tag-Assisted Peptide Synthesis (TAPS), and Solid-Phase Peptide Synthesis (SPPS)?

Liquid phase peptide synthesis (LPPS), tags-assisted peptide synthesis (TAPS) and solid-phase peptide synthesis (SPPS) are three primary synthetic methods for creating peptides, each with distinct differences.

LPPS synthesizes peptides in solution, using classic organic chemistry tools. This method is cost-effective, scalable, and most environmentally friendly, making it ideal for shorter peptides. However, LPPS can encounter difficulties with longer peptides due to challenges in maintaining consistent reactions, solubility and removing unwanted byproducts.

TAPS also synthesizes peptides in solution but uses organic tags to aid in solubility and the separation of peptides from reagents and byproducts. This makes TAPS also cost-effective, scalable, and more environmentally friendly than SPPS, ideal for short-to-medium sized peptides.

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 Tag-Assisted Peptide Synthesis?

TAPS involves building peptides step-by-step in solution. Here’s a detailed look at the process:

1. 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.
2. Coupling: The activated amino acid is then combined with another amino acid to form a peptide bond. In the initial step, the first amino acid is coupled onto the soluble tag instead of another amino acid. This stage is repeated sequentially, adding one amino acid at a time to extend the peptide chain.
3. 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.
4. Final deprotection: The final step involves removing any remaining protective groups and cleavage from the tag, to obtain the finished peptide in its active form.
5. Purification: After the peptide chain is fully assembled and removed from its tag, 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.

Why choose our Peptide synthesis services?

Bachem has 50 years of leadership in taking peptide breakthroughs from discovery to commercialization. We offer comprehensive services including research and GMP-grade materials, process development, and analytical support across all clinical phases.

Our innovative technologies include Tag-Assisted Peptide Synthesis (TAPS) and oligonucleotide synthesis (TAOS), continuous chromatography (MCSGP), stirred-bed technology (SBT), 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 prioritize 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 global leadership, innovative technologies, comprehensive services, and commitment to quality.