An Integrated Approach to Cyclic Peptide Drug Discovery

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When it comes to drug discovery projects we often need to be flexible and agile to meet the demands of the project. This case study showcases how working as a part of an integrated team we swiftly tested compounds and produced data to feed the design-make-test cycle. 

Challenges

This project required swift turn around between purification and biological and ADME testing, enabling the data to feed into the design-make-test cycle efficiently. A further complication to this was the complex chemistry, which often meant low quantities of purified final product was produced.

Design make test understand cycle

What We Did...

Example Peptide Workflow

Integrated Cyclic Peptide Drug Discovery

Figure 1. An example of the synthetic chemistry workflow during an integrated peptide project. Designed to maximize outputs from the project and ensure biological testing is efficient . 

An Integrated Approach

Co-located teams facilitate our streamlined approach to integrated projects. During the course of this cyclic peptide project we were able to:
  • Generate up to 20 linear sequences per week at 0.1 – 1.2 mmol scale with up to >95% purity by UPLC-MS
  • The in house dedicated purification team were able to clean crude peptides of <5% purity up to >95% by reverse phase preparative HPLC
  • We afforded up to >30 isolated, complex cyclic peptides per month
  • Rapidly synthesize and isolate purified peptides in as little as one week from resin loading
  • Streamlined integration with Biology/DMPK – biological profiling of target compounds were achieved in the same week of synthesis (i.e. isolated on Thursday, biochemical data provided to client on Friday)
  • Biology and DMPK teams were able to share stock solution of peptide for profiling and can use as little as 500 µg (biochemical, ksol, and chromlogD7.4 assays)

Summary

With Bioscience, Chemistry and ADME/DMPK teams all under one roof we were able to successfully purify and deliver compound data within 24 hours. Due to the nature of the chemistry it was sometimes difficult to produce more than 0.5 mg of the compounds however being on one site enabled our teams to share a stock solution.  
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