Application of gel-phase 19F 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 19F 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(psiMe, Me pro)-OH as a backbone-protecting group was found to be superior according to gel-phase 19F NMR spectroscopy. Implementation of the optimized Fmoc protocol enabled an effective synthesis of signal peptide LLLLTVLTV.
Pudelko
Maciej
M
Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
Kihlberg
Jan
J
Elofsson
Mikael
M
D000951:Antigens, Neoplasm / Q000737:chemistry; D006801:Humans; D018396:Mucin-1; D009077:Mucins / Q000138:chemical synthesis* / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D021382:Protein Sorting Signals
D000951:Antigens, Neoplasm; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; D009842:Oligopeptides; D021382:Protein Sorting Signals