Chimica Oggi-Chemistry Today
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Recent advances in peptide drug discovery and development; a Key-role for peptide synthesis technology
Applications and Sales Manager, Protein Technologies, Inc.

KEYWORDS: Peptides, peptide synthesis, difficult sequences, proteins, protein synthesis, induction heating.

With higher rates of success in the clinic than small molecules, and properties uniquely suited to addressing current targets of interest, the reasons for continued investment into peptide therapeutics in the biopharmaceutical sector are clear. Concurrently, improvements in the technology for peptide synthesis have facilitated the exploration of new therapeutic mechanisms of action, the design of peptides with improved pharmacokinetic properties, and the implementation of the most efficient methods for process development.


Great opportunities remain, and investment continues, in the modulation of G Protein Coupled Receptors (GPCRs) by peptides. Marketed GLP-1R agonists clearly represent a recent success story of peptide therapeutic development. Yet recently there is much excitement surrounding novel therapeutic applications like immuno-oncology, in which targeted immunotherapies may be generated from peptides found in the tumor cells of patients. High-throughput instrumentation like the Symphony XTM synthesizer has helped teams working in this area to quickly and cost-effectively obtain libraries of hundreds of peptides that are crucial in the development and validation of these therapies.     
Peptide drug discovery and development is also focused increasingly on exploring complex and modified peptides that provide improved bioavailability, stability, and intellectual property potential. Many researchers are examining the combination of cyclization and other modifications like N-methylation. Owing to steric and conformational factors, the preparation of these modified peptides can be synthetically challenging, so enabling technologies like rapid heating methods have become important. Parallel and independent induction heating on multiple vessels on the Prelude X™ peptide synthesizer has been applied for the simultaneous synthesis at multiple temperatures (1) of difficult peptides and for the preparation of cyclic peptides (2). In both examples, multiple temperature profiles were tested in parallel.
By providing the ability to simultaneously screen multiple temperatures in order to optimize this parameter, the instrument fits well within a design of experiments (DoE) approach to process development. The integration of DoE has been a significant advancement in peptide process development and manufacturing of recent years. Typically facilitated by the use of commercially available software platforms, when implemented correctly DoE can lead to optimized process solutions more quickly and economically than traditional methods. This, along with recent regulatory guidance on peptides, has led peptide-focused contract manufacturing and process development groups to embrace the DoE concept for identifying key process parameters and defining their optimal operating ranges.


Interest in the development of peptides remains strong, particularly given their application in novel therapeutic approaches and a growing arsenal of design and delivery methods for overcoming their potential liabilities as drugs....In order to continue reading this article please register to our website – registration is for free and no fees will be applied afterwards to download contents.

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