Research Scale Peptide Synthesizer Comparison - A Guide to Choosing a System that Fits Your Needs

We've gathered the key things to know to adequately compare the most popular synthesizers on the market for users searching for a peptide synthesizer.

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Introduction

A major reason medicinal chemists and researchers love peptides is they offer a unique ability to treat unmet clinical needs in comparison to small molecules and biological therapeutics. With over 70 approved peptide therapeutics on the market treating patients today, researchers are looking for the next peptide therapeutic that will make waves.

What about synthesizing the peptides that researchers use for their studies? CSBio has been making peptides and peptide synthesizers for over 25 years, and we’ve developed synthesizers for the first-time peptide synthesis user as well as the advanced peptide chemist. Here’s the major things to consider when comparing research scale peptide synthesizers for your needs.

1. Manual, Semi Automated, or Fully Automated?

Many companies market peptide synthesizers without specific details around the level of automation the system performs, but there can be a significant difference between peptide synthesizers. This is one of the most important factors in choosing a peptide synthesizer.

For those that haven’t made a peptide before, a typical solid phase peptide synthesis protocol will consist of deprotection cycles, multiple washes, coupling, and more multiple washes for each amino acid addition to their peptide. There is typically a combined total of 10 washes and deprotection cycles to ensure adequate synthesis, defined by high purity of the targeted peptide being synthesized.

Typical Peptide Synthesis Cycle for each Amino Acid Addition:

  1. 2x Deprotection
  2. 6x DMF Wash
  3. Coupling
  4. 2x DMF Wash

When performing manual synthesis, the washes and deprotection cycles are extremely redundant and time consuming, requiring manual solvent addition and draining for each wash or deprotection cycle. Many peptide synthesizers on the market today only perform the coupling step, and require users to manually perform the remainder of the synthesis. Given the coupling step is the least labor intensive portion of the synthesis and accounts for less than 10% of the touch time, these peptide synthesizers are categorized as manual synthesizers.

What does it mean to have a fully automated peptide synthesizer? Most peptide sequences are in the 20 to 30 amino acid length range, and users would like to be able to setup and walk away from their peptide synthesizer and come back to a completed peptide. This means the synthesizer is able to fully automate the completion of a synthesis cycle for each amino acid, as well as continue to subsequent amino acids without any user intervention such as adding more solvents, reagents, or amino acids.

Peptide Synthesizer Comparison - Manual vs. Automated Synthesizers

Peptide Synthesizer Comparison - Manual vs. Automated Synthesizers

There are some semi-automated peptide synthesizers which are able to automate a synthesis cycle, however have limited unattended amino acid positions. Systems such as these would require the user to come back in set intervals depending on the length of the peptide the user is synthesizing.

Take a look at our case study of the synthesis of a 132-mer peptide on CSBio’s research scale peptide synthesizers, which was performed entirely unattended over 3 days without any solvent recharging, amino acid additions, or manual steps.

Peptide Synthesizer Comparison - Automated Research Scale Synthesizers

Peptide Synthesizer Comparison - Automated Research Scale Synthesizers

2. Reaction Vessel (RV) Size

The reaction vessel size determines the maximum synthesis scale that a peptide synthesizer is capable of performing, and synthesis scale determines the amount of peptide material that can be produced per synthesis batch. Most peptide synthesizers consider the solvent, reagent, and amino acid consumption based on the reaction vessel size to ensure adequate unattended automation; as users would not want a reaction vessel sized on a synthesizer that requires solvent addition every 30 minutes.

Dependent on what quantities (mg to grams) a user requires at their phase of research, determines the size of reaction vessel. The amount of peptide that can be produced in any given reaction vessel can depend on many factors including resin substitution, chemistry, number of amino acid additions, and expected growth. But to provide a rough idea, a 15ml reaction vessel can be used to produce anywhere from 50mg to 500mg dependent on these many factors. For a 20-mer peptide, using 0.6 mmol/gram substitution resin, a 0.3mmol synthesis can be performed with a 15ml reaction vessel producing approximately 500mg of crude peptide. Upon purification, dependent on purity requirements, 500mg of crude peptide can generally easily translate to 150mg of pure peptide.

3. Chemistry Flexibility

For most users making peptides, the desired goal is to simply produce their target peptide, where having an easy to use peptide synthesizer is more desirable than having a lot of features which can increase flexibility, but also add complexity.

For the advanced peptide chemist, there may be a desire to have a lot of flexibility in performing different types of chemistry to improve synthesis yield, or to be able to develop a process for scale up. This flexibility could be performing double couplings, cappings, doing Fmoc synthesis, Tboc synthesis, using DIC coupling or HBTU coupling within the same peptide, to name a few.

While there are many detailed factors to consider that will drive this flexibility, primarily related to the software interface and how system functions are performed, the major factor is whether the system has the dedicated reagent bottles available. To perform DIC coupling on one amino acid addition, followed by HBTU coupling on the subsequent amino acid addition in the peptide sequence, requires the dedicated reagent bottles to be able to perform this in a fully automated mode.

These are the top 3 things to consider when looking for a research scale peptide synthesizer. There are many other considerations as well, such as:

  • Crude purity yield that the synthesizer is capable of producing
  • Performing heated synthesis which allows for faster synthesis times
  • Performing parallel synthesis which allows for multiple peptides to be made at once
  • Synthesizer reliability, ease of repair and maintenance, and long term costs associated with ownership
  • Scale up considerations, where users will desire to establish processes on research scale systems to move towards pilot and commercial scale peptide production.

Reach out to us at instrument@csbio.com, schedule a call to learn more, or just ring us directly at +1 650 525 6200 if you’re interested in discussing your peptide synthesizer needs.

About CSBio: For over 25 years, CSBio, a leading peptide and peptide synthesizer manufacturing company located on the edge of Silicon Valley in Menlo Park, California, has been providing high quality custom peptides, cGMP peptides and automated peptide synthesizers to the global pharmaceutical community. CSBio’s peptide products and peptide synthesizers can be found in production laboratories, universities, and pharmaceutical companies worldwide.

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About Us

CSBio is a leading peptide and instrumentation manufacturing company located on the edge of Silicon Valley in Menlo Park, California.

CSBio provides nonGMP and cGMP peptides, peptide APIs, research scale peptide synthesizers, commerical scale peptide synthesizers, DNA/RNA oligonucleotide synthesizers, and preparative HPLC purification equipment.

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