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Synthesis of complex cyclic peptide containing non- canonical amino acids
Project overview
The challenge
Synthesizing 200+ cyclic peptides with complex modifications, under tight timelines, while overcoming purification and synthetic hurdles.
Our solution
Tailored synthetic strategies, optimized cyclization techniques, and an integrated purification workflow.
Our impact
Delivered >200 high-purity peptides in 8 months, overcoming synthesis challenges and enabling rapid drug discovery progression.
Read on for a detailed case study below
The challenge
Cyclic peptides offer improved stability and bioavailability but require precise cyclization strategies and specialized synthetic techniques to maintain biological activity. The key challenges in this program included:
- Scale and speed – Synthesizing 200+ complex cyclic peptides within tight timeframes.
- Non-canonical amino acids – Incorporating complex, customized amino acids requiring pre-synthesis before SPPS.
- Synthetic difficulties – Managing stereochemistry, ring strain, racemization, and diketopiperazine formation.
- Purification bottlenecks – Processing crude peptides (<5% purity) to final products (≥95% purity) efficiently.
Our approach
We applied a tailored chemistry and purification strategy, ensuring efficiency at every step:
- Resin selection expertise – Chose optimal resins based on peptide properties for high synthetic efficiency.
- Optimized cyclization – Selected the best approach (on-/off-resin) to maximize yield and purity.
- Cross-functional collaboration – Chemists and purification specialists worked closely to streamline workflows.
Our solution
We implemented a comprehensive synthetic and purification workflow to efficiently produce high-quality cyclic peptides:
- Customized SPPS strategy – Automated for routine peptides, manual for challenging sequences.
- Diverse cyclization techniques – Including click reactions, alkylations, and on-resin modifications.
- Mitigating synthetic hurdles – Adapting conditions to overcome racemization and ring strain issues.
- Integrated purification process – Rapid transition from crude peptides to purified compounds meeting biological testing standards.
The result
By combining chemistry expertise with process efficiency, we delivered over 200 high-quality cyclic peptides, accelerating drug discovery efforts:
- 200+ peptides delivered in 8 months – Meeting all project deadlines.
- ≥95% purity achieved – Through streamlined purification strategies.
- Seamless incorporation of non-canonical amino acids – Overcoming synthesis challenges.
One-week turnaround per peptide – Enabled by optimized workflows and close team collaboration.
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