Fully Automated Sequence-Specific Synthesis of α-Peptides Using Flow Chemistry
- Resource Type
- Article
- Authors
- Knudsen, Kristian; Ladlow, Mark; Bandpey, Zhale; Ley, Steven
- Source
- Journal of Flow Chemistry; January 2014, Vol. 4 Issue: 1 p18-21, 4p
- Subject
- Language
- ISSN
- 2062249X; 20630212
The efficient and convenient synthesis and manipulation of the peptides beyond what is normally feasible to achieve in a living cell offers a powerful strategy for investigating the complex processes that occur in living organisms and may lead to elucidation of mechanisms that are of direct relevance to new drug discovery initiatives. We report an efficient and sequence-specific stop flow strategy for the synthesis of α-peptides using natural amino acids as well as synthetic amino acid analogues, activated as N-carboxyanhydrides with traceless protection groups. The coupling step is carried out by a robotic liquid handler and by maintaining the product in the liquid phase we have overcome several challenges posed by traditional peptide synthesis. The removal of the protection group uses a continuous flow hydrogenolysis method for highly efficient deprotection. We demonstrate that high yields and purities are obtainable via this new automated solution-phase approach that runs under a dedicated software control. This technique opens up new possibilities for development of peptides for various pharmaceutical and proteomic applications in routine research laboratories.