High-throughput synthesis of conopeptides: a safety-catch linker approach enabling disulfide formation in 96-well format
Article first published online: 7 DEC 2006
Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd.
Journal of Peptide Science
Volume 13, Issue 2, pages 133–141, February 2007
How to Cite
Brust, A. and Tickle, A. E. (2007), High-throughput synthesis of conopeptides: a safety-catch linker approach enabling disulfide formation in 96-well format. J. Peptide Sci., 13: 133–141. doi: 10.1002/psc.825
- Issue published online: 23 JAN 2007
- Article first published online: 7 DEC 2006
- Manuscript Accepted: 24 OCT 2006
- Manuscript Received: 9 OCT 2006
- solid-phase peptide synthesis;
- disulfide bonds;
- safety-catch linker;
- high-throughput synthesis
Conotoxins exhibit a high degree of selectivity and potency for a range of pharmacologically relevant targets. The rapid access to libraries of conotoxin analogues, containing multiple intramolecular disulfide bridges for use in drug development, can be a very labor intensive, multi-step task. This work describes a high-throughput method for the synthesis of cystine-bridged conopeptides.
Peptides were assembled on a peptide synthesizer employing the Fmoc solid-phase strategy using a safety-catch amide linker (SCAL). Side-chain protecting groups were removed on solid phase before SCAL activation with ammonium iodide in TFA, finally releasing the peptide into the TFA solution. Disulfide bond formation was performed in the cleavage mixture employing DMSO.
This improved method allows mixtures of oxidized peptides to be obtained in parallel directly from a peptide synthesizer. A single HPLC purification of the resulting crude oxidized material produced peptides of >95% purity. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd.