Improved Fmoc Deprotection Methods for the Synthesis of Thioamide-Containing Peptides and Proteins

James Petersson presents the Fmoc deprotection for peptides and proteins containing thioamides.

Thieme Chemistry Journals Awardees – Where Are They Now? Improved Fmoc Deprotection Methods for the Synthesis of Thioamide-Containing Peptides and Proteins: D. M. Szantai-Kis, C. R. Walters, T. M. Barrett, E. M. Hoang, E. J. Petersson
Synlett 2017, 28, DOI: 10.1055/s-0036-1589027

Site-specific incorporation of thioamide bonds as bioisosteric replacement of native peptide (amide) bonds is a very useful strategy for producing peptide and protein mimics having distinctive biological, structural and physico-chemical properties. Unfortunately, the use of conventional Fmoc-peptide synthesis is challenging when it comes to incorporating thioamides. The group of Professor E. James Petersson from the University of Pennsylvania (Philadelphia, USA) has recently reported a novel method based on the use of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) rather than piperidine in Fmoc deprotection, as this reduces epimerization and increases yields of thioamide-containing peptides. 

Professor Petersson said: “Our new synthetic protocol will improve yields of thioamide modifications in peptides and proteins, enabling a variety of applications, from fluorescence biophysics studies of protein folding to stabilizing therapeutic peptides in vivo.”