Therapeutic Peptides Upstream Synthetic Process Development

Large-scale peptide production requires the development of robust production processes and their optimization to enable large-scale production under more efficient and lower-cost conditions. CD Formulation's peptide synthesis experts provide efficient, robust, and scalable upstream synthetic peptide process development services for clinical manufacturing, process validation, etc. We have extensive expertise in developing complex peptide production methods and can help find the best way to produce peptides to reduce costs and achieve the required quality.

Current Peptide Synthetic Manufacturing Processes

Chemical synthesis is the preferred method for producing peptide therapeutics under development, and this synthesis can be performed in solid or liquid phase, namely solid phase peptide synthesis (SPPS) and liquid phase synthesis (LPPS). Both methods are based on a similar reaction mechanism, where the amino acids and/or fragments of the desired peptide are sequentially added to a mixture to react with the growing chain.

• Solid Phase Peptide Synthesis (SPPS): The peptides are synthesized on solid support (usually resin beads). SPPS involves the reaction of one N-protected amino acid with the peptide chain immobilized on the solid support (resin), followed by the deprotection of the terminal amino acid. The next amino acid then undergoes the same process. After the procedure is terminated and all amino acids have reacted, the peptide is released from the resin in a cleavage step
• Liquid Phase Peptide Synthesis (LPPS): LPPS is a synthesis method performed in solution, usually using free amino acids for synthesis. This method involves multiple repetitions of the coupling and deprotection steps of the amino acids until the desired peptide sequence is complete. In liquid phase synthesis, steps such as the protection of functional groups and activation of amino acids need to be considered. Compared with SPPS, LPPS may be more suitable for synthesizing shorter peptide sequences.

Fig. 1 Illustration of solid vs liquid phase peptide synthesis cycles. (Kekessie I, et al., 2024)

Explore Our Therapeutic Peptides Upstream Synthetic Process Development Services

CD Formulation is an expert in peptide synthesis, with a proven track record and deep expertise in robust process development and optimization of peptide molecules, understanding the nature of any impurities that may be introduced during production and understanding how to reduce their generation, thereby significantly improving yields.

We have a dedicated peptide laboratory to support peptide synthesis, downstream purification, isolation, and lyophilization to help you make the following key decisions before large-scale peptide synthesis:

• Support process validation.
• Support large-scale manufacturing.
• Support the delivery of process development projects at all stages of clinical development.

When you need a peptide, our peptide scientists will evaluate the sequence and determine the synthesis strategy based on knowledge and experience to handle all forms of peptide synthesis (i.e. solid, solution, or mixed phase peptides). Our peptide synthesis process development services include:

Fig. 2 Types of process development for therapeutic peptide synthesis. (CD Formulation)

Solid Phase Peptide Synthesis (SPPS) Process Development

Peptides are usually synthesized by solid phase peptide synthesis (SPPS), which has the advantages of high efficiency/high selectivity and high purity. Our scientists have synthesized various types of peptides using SPPS technology, including linear peptides, cyclic peptides and modified peptides.

In this process, we can add different protecting groups and functional groups as needed to control the rate and selectivity of the synthesis reaction. We can also use high-performance liquid chromatography (HPLC) and mass spectrometry analysis techniques to purify and identify the synthesized products to ensure that the purity and structure of the final product meet the requirements.

Key decision steps in our solid phase peptide synthesis process:

• Selection of suitable solid phase carrier.
• Optimization of reaction conditions.
• Selection of protecting groups and deprotection methods.
• Cargo separation and purification.
• Deprotection and release of the final peptide chain.

Liquid Phase Peptide Synthesis (LPPS) Process Development

The liquid-phase peptide synthesis process is a method for synthesizing peptides in solution. It is an efficient and flexible synthesis method suitable for synthesizing peptides of various lengths and structures.

In the liquid-phase peptide synthesis process, we usually use Fmoc (9-fluorenylmethyloxycarbonyl) or Boc (tert-butyloxycarbonyl) as a protecting group, and gradually synthesize the target peptide by alternating the addition, deprotection and coupling reactions of amino acids. Importantly, our scientists can design and optimize the liquid-phase peptide synthesis process according to your needs to ensure high-purity and high-yield products.

Key decision steps in our liquid phase peptide synthesis process:

• Selection of appropriate protecting groups and deprotection conditions.
• Optimization of amino acid coupling reactions.
• Control of synthesis reaction conditions.
• Monitoring and optimization of the synthesis process to improve purity and yield.

Mixed Phase Peptide Synthesis Process Development

Mixed phase peptide synthesis is a method for synthesizing complex peptides by combining different reaction conditions to improve the purity and yield of the product. In the mixed-phase peptide synthesis process, the solid-phase synthesis method is usually used, that is, the peptide chain is fixed on the resin, and then the amino acid monomers are gradually added in a step-by-step reaction to extend the peptide chain.

When developing the mixed-phase peptide synthesis process, our scientists comprehensively consider a variety of factors, including reaction conditions (such as temperature, solvent, catalyst, etc.), reaction time, activity and purity of amino acid monomers, resin selection, protection group strategy, reaction sequence, etc. By optimizing these factors, we can improve the efficiency and yield of synthetic peptides while ensuring the purity and structural correctness of the products.

In addition to the typical chemical synthesis process development mentioned above, we also provide innovative biosynthesis process development services, including fermentation synthesis, enzymatic synthesis, and genetic engineering synthesis.

Types of Synthetic Peptides We Can Handle

• Linear and branched peptides up to 40 AA (natural and non-natural).
• Peptide derivatives.
• Peptides with multiple disulfide bonds, head-to-tail cyclization, and side-to-side cyclization.
• Fluorescently labeled peptides.
• Cysteine-rich peptides.

Types of Peptide Synthesis Impurities We Can Handle

The peptide synthesis process is relatively complex, and the types of impurities involved are diverse. Our team of impurity analysis experts can develop a variety of control strategies to monitor and eliminate these impurities at different stages of synthesis to ensure the purity and quality of the final product. The types of peptide synthesis impurities we can handle include:

• Process-related impurities: Missing (incomplete) peptides, cleaved peptides, deamidated peptides, byproducts formed by incomplete deprotection of amino acid side chains, oxidized peptides, products of disulfide bond exchange, diastereomeric peptides, oligomers and/or polymers.
• Degradation impurities: Hydrolysis products, cleaved peptides, oxidized/reduced peptides, polymers.
• Residual solvents: Acetonitrile, DMF, pyridine.
• Elemental impurities: Fluoride, heavy metals.
• Genotoxic impurities: Carbodiimide compounds.

Our Peptide Synthesis Equipment and Impurity Analysis Equipment

• Automated peptide synthesizer.
• Liberty pro peptide synthesizer.
• Microwave-assisted peptide synthesizer.
• Tangential flow filtration.
• LC-MS, GC-MS, MALDI Tof.
• Multi-angle light scattering (MALS) detector.
• Circular dichroism (CD) analysis.
• Nuclear magnetic resonance spectroscopy.
• Post-column derivatization amino acid analyzer.

Why Choose Us for Therapeutic Peptides Upstream Synthetic Process Development?

• Our team of experienced scientists and researchers have extensive knowledge and expertise in peptide synthesis, purification, and analytical methods.
• We have a proven track record of successfully developing efficient and scalable synthetic processes for therapeutic peptides.
• Our synthetic peptides lab is equipped with the latest technology and equipment for peptide synthesis, purification, and analysis, allowing us to conduct high-quality research and development work, ensuring the success of our clients' projects.
• We adhere to strict quality assurance protocols throughout the entire upstream synthetic process development, ensuring the consistency, purity, and quality of the peptides we produce.
• We provide flexible experimental options to meet the needs of different customers.

Publication

CD Formulation is committed to providing our clients with the best-in-class peptide process development and production services to meet their specific needs. Our team of experts can assist in optimizing peptide synthesis, purification, and analysis processes to ensure high purity and yield of the final product. Please don't hesitate to contact us if you are interested in our services. We look forward to cooperating with you.

How It Works

STEP 1

Submit a service request describing your specific research or development need.

STEP 2

We'll email you to provide your quote and confirm order details if applicable.

STEP 3

Execute the project with real-time communication, and deliver the final report promptly.