Application of gel‐phase 19 F NMR spectroscopy for optimization of solid‐phase synthesis of a hydrophobic peptide from the signal sequence of the mucin MUC1

This paper describes the manual Fmoc/ t ‐Bu solid‐phase synthesis of a difficult nine‐residue hydrophobic peptide LLLLTVLTV from one of the signal sequences that flank the tandem repeat of the mucin MUC1. Gel‐phase 19 F NMR spectroscopy was used as a straightforward method for optimization of the solid‐phase synthesis. Different approaches were applied for comparative studies. The strategy based on modified solid‐phase conditions using DIC/HOAt for coupling, DBU for Fmoc deprotection, and the incorporation of the pseudo proline dipeptide Fmoc‐Leu‐Thr(ψ Me , Me pro)‐OH as a backbone‐protecting group was found to be superior according to gel‐phase 19 F NMR spectroscopy. Implementation of the optimized Fmoc protocol enabled an effective synthesis of signal peptide LLLLTVLTV. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.