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Automated Solid-Phase Peptide Synthesis Technology

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Automated solid-phase peptide synthesis is a fast and convenient method for the simultaneous synthesis of multiple peptides, providing a suitable technology for the production of chemically engineered peptides. CD Formulation uses advanced automated solid phase peptide synthesis technology to efficiently synthesize multiple peptides simultaneously with precise control over sequence and modifications, meeting the needs of different customers.

About Automated Solid-Phase Peptide Synthesis Technology

Automated solid-phase peptide synthesis involves joining multiple amino acids via peptide bonds to produce peptides. The process mimics biological processes for producing long peptides. In solid-phase peptide synthesis (SPPS), peptides are "immobilized" on a solid surface and can remain while liquid-phase reagents and synthesis byproducts are washed away. SPPS also allows for the synthesis of natural peptides that are difficult to express in bacteria, the incorporation of unnatural amino acids, and peptide backbone modifications. In addition, the process allows for the synthesis of protein D, produces extremely high yields at each step, and provides a solution to the problems associated with sequence-dependent synthesis.

Fig. 1 Automated solid-phase peptide synthesizer.Fig. 1 Schematic representation of Boc-SPPS (A) and the first automated solid-phase peptide synthesizer (B). (Tian J, et al., 2022)

Our Services Related to Automated Solid-Phase Peptide Synthesis

Peptide synthesis is a very delicate, complex, and time-consuming process. Many labs are turning to automated microarray printers to help streamline the process.

The original method used a polystyrene resin, prepared to contain chloromethyl (-CH2Cl) groups approximately one in every hundred benzene rings, and then attached a Boc-protected C-terminal amino acid to the resin via an SN2 reaction to form an ester bond.

Once the first amino acid is bound to the resin, four more steps are repeated to build the peptide.

Fig. 2 Peptide assembly.Fig. 2 Peptide assembly by SPPS. (Mäde V, et al., 2014)

At CD Formulation, we use fully automated solid-phase synthesizers to automatically repeat the coupling, washing, and deprotection steps for different amino acids. The yields are high at each step, and mechanical losses are minimized because the peptide intermediates are not removed from the insoluble polymer until the last step. Typically, peptides containing 20 amino acids can be prepared in a few hours.

Our Equipment

Peptide Microarray Spotter

The peptide microarray spotter is a liquid handling platform for performing automated solid-phase peptide synthesis. The system spots Fmoc or t-Boc amino acid residues in dimethylformamide (DMF) onto a solid surface such as a membrane, glass slide, or any other suitable array surface in a user-defined order.

The device automates solid-phase peptide synthesis in a simple and reproducible manner with high yield and accuracy.

High-Throughput Automated Continuous Peptide Synthesizer

The device offers significant advantages for peptide production by using high-throughput automation for continuous SPPS. Up to 24 peptides can be synthesized per batch with higher purity, less waste, and fast speed. Compared to parallel methods, individual peptides in a batch can be conveniently analyzed and purified without waiting for the entire batch to be completed.

Advantages of Automated Solid-Phase Peptide Synthesis Technology

  • The chemical reactions required to assemble the peptides can be performed simultaneously in a large number of reaction tubes, thus enabling parallel and multiplexed syntheses.
  • No intermediate purification step is required, as only simple washing of the resin is required after the coupling or deprotection step.
  • The possibility of using excess reagents helps to increase the yield of the synthesized peptides.
  • Faster reaction times greatly reduce the operation time.

Custom Automated Solid-Phase Peptide Synthesis Services

Therapeutic Peptide Synthesis and Production

Many peptide drugs are developed by chemically modifying natural molecules or by artificial synthesis. CD Formulation has extensive experience in custom therapeutic peptide synthesis and production. Each synthesis step is subject to our strict quality control. We can produce various synthetic peptides according to customer requirements, from simple to long and challenging sequences. Leverage our best-in-class automated SPPS technology to support the synthesis of your target peptides.

Deliverables

CD Formulation's peptides are delivered as lyophilized powders and packaged in separate sample tubes according to customer requirements. To ensure the quality of the peptides, we also provide the following documents for your reference:

  • HPLC/MS Test: All peptides we produce are tested by MS and HPLC to ensure the accuracy of the peptide products.
  • COA Document: We provide a COA document for each peptide, including the shape and appearance of the peptide sample, delivery specifications, molecular weight, and purity.
  • Solubility Test: This is optional. We provide two solubility testing services according to customer requirements: qualitative dissolution test and quantitative dissolution test.

Publication

Published Data

Technology: Automated Solid-Phase Peptide Synthesis

Journal: J Pept Sci.

IF: 1.78

Published: 2023

Results:

The authors developed an optimized automated two-step method for the synthesis of structurally diverse triazole peptide mimetics. Different conditions were explored for their adaptability to the automated reaction apparatus, with particular emphasis on the desired long-term stability of the diazo transfer reagent and Cu(I) catalyst in solution. ISA·HCl was shown to be the reagent of choice for the diazo transfer reaction. [Cu(CH 3 CN) 4 ]PF 6 was used as the catalyst and TBTA as the stabilizer to prevent oxidation to Cu(II). Five triazole peptidomimetics (8–5 amino acid residues) were efficiently synthesized under the optimized conditions using two different resins. Analysis of the crude products by HPLC-MS showed moderate to good purity (70–85%) of the desired triazole peptidomimetics. Synthesis times ranged from 9 to 12.5 h.

Fig. 3 Two general strategies to synthesize alpha-amino alkynes.Fig. 3 Representation of the two general strategies to synthesize α-amino alkynes starting from amino acids. (Guarrochena X, et al., 2023)

CD Formulation is designed to provide powerful tools for handling the synthesis of peptides of varying lengths and complexities. Please feel free to contact us if you are interested in our services. Learn how our automated SPPS technology can support your custom peptide synthesis projects.

References

  1. Tian J, Li Y, Ma B, et al. Automated Peptide Synthesizers and Glycoprotein Synthesis. Front Chem. 2022 May 5;10:896098.
  2. Mäde V, Els-Heindl S, Beck-Sickinger AG. Automated solid-phase peptide synthesis to obtain therapeutic peptides. Beilstein J Org Chem. 2014;10:1197-1212.
  3. Guarrochena X, Kaudela B, Mindt TL. Automated solid-phase synthesis of metabolically stabilized triazolo-peptidomimetics. J Pept Sci. 2023;29(9):e3488.
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CD Formulation is an expert in formulation science and pharmaceutical process development in therapeutic proteins & peptides, dedicated to supporting biotherapeutics development and production...

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