Cyclic peptides offer enhanced stability and bioavailability, but precise cyclization strategies and specialized synthetic techniques are required to maintain their biological activity. A recent project undertaken by Concept Life Sciences highlighted some of these key challenges, including:
- Scale and speed – Synthesizing over 200 complex cyclic peptides within tight timelines
- Non-canonical amino acids – Incorporating customized amino acids that needed to be pre-synthesized prior to solid-phase peptide synthesis (SPPS)
- Synthetic complexity – Addressing issues such as stereochemistry control, ring strain, racemization, and diketopiperazine formation
- Purification bottlenecks – Efficiently purifying crude peptides with initial purities below 5 % to achieve final purities of 95 % or higher
Image Credit: Concept Life Sciences
Concept Life Sciences’ approach
To overcome these challenges, Concept Life Sciences applied a tailored chemistry and purification strategy designed to ensure efficiency at every step. This relied upon:
- Resin selection expertise: Selected optimal resins based on peptide properties to maximize synthetic efficiency
- Optimized cyclization: Chose the most effective cyclization approach (on- or off-resin) to improve yield and purity
- Cross-functional collaboration: Chemists and purification specialists worked closely to streamline workflows and accelerate delivery
Concept Life Sciences’ solution
A comprehensive synthetic and purification workflow was implemented to efficiently produce high-quality cyclic peptides. This included:
- A customized SPPS strategy, including manual methods for challenging sequences and automated methods for routine peptides
- Diverse cyclization techniques, including alkylations, on-resin modifications, and click reactions
- Mitigation of synthetic hurdles, including adaptation of conditions to overcome racemization and ring strain issues
- An integrated purification process, enabling the rapid transition from crude peptides to purify compounds while continuing to adhere to biological testing standards
Image Credit: Concept Life Sciences
Project results
Concept Life Sciences successfully delivered more than 200 high-quality cyclic peptides, combining chemistry expertise with process efficiency to accelerate drug discovery efforts. This resulted in:
- On-time delivery: Over 200 peptides synthesized and delivered within 8 months
- High purity: Achieved ≥95 % purity through streamlined purification strategies
- Synthetic success: Effectively incorporated non-canonical amino acids despite complex synthesis requirements
- Rapid turnaround: Optimized workflows and close team collaboration enabled a consistent 1-week turnaround per peptide
About Concept Life Sciences
Concept Life Sciences is a leading contract research organisation (CRO) serving the global life sciences industry. For over 25 years, the company, and its heritage companies, have provided consultative and collaborative drug discovery and development services. Our approach, supported by passionate scientists and world-leading capabilities, enables clients to overcome complex scientific challenges across a broad range of therapeutic areas, improving program success rates. The company has successfully helped 29 candidates advance to the clinic.
The company offers sophisticated translational biology services coupled with exceptional end-to-end chemistry capabilities across all modalities, including small molecules, biologics, peptides and cell & gene therapies, with the ability to seamlessly integrate capabilities and provide bespoke solutions to address client needs.
Collectively, the company’s high-quality services and commitment to customer service across the drug development pathway enhance efficiency in drug discovery, helping clients advance their drugs to clinic in as little as 32 months, well ahead of the industry average of 60 months.
Driven by a passion for science, Concept Life Sciences has around 230 employees, with around 70% holding PhDs. The company operates from state-of-the-art UK facilities, headquartered near Manchester, with additional operations in Edinburgh, Dundee, and Sandwich. The headquarters is one of the UK’s largest medicinal chemistry CRO sites with key discovery services all under one roof.
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