Native chemical ligation of hydrophobic peptides in organic solvents

• Published in: Journal of peptide science Vol. 16; no. 10; pp. 558 - 562
• Main Authors: Dittmann, Marc, Sauermann, Jörg, Seidel, Ralf, Zimmermann, Wolfgang, Engelhard, Martin
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-10-2010
• Subjects: Dimethylformamide; Dimethylformamide - chemistry; hydrophobic peptides; Hydrophobicity; ligation in organic solvents; Lithium chloride; peptide synthesis; Peptides - chemistry; Solubility; Solvents; Solvents - chemistry; transmembrane proteins; Water - chemistry
• ISSN: 1075-2617; 1099-1387; 1099-1387
• DOI: 10.1002/psc.1285

The application of chemistry to hydrophobic peptides and membrane‐spanning helices is hampered by the fact that they are only poorly soluble in aqueous buffers and that they have a tendency for aggregation. These properties lead to difficulties when purifying them after chemical synthesis and particularly interfere with native chemical ligation. Here, we describe native chemical ligation of model peptides in the organic solvent dimethylformamide (DMF) under anhydrous conditions. Best results concerning yields and complete solubility are obtained if thiophenole is used in the presence of LiCl. These conditions might be applicable also for the ligation of transmembrane helices. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.
Native chemical ligations can be carried out efficiently and fast in organic solvents like dimethylformamide. These conditions are suitable for the synthesis of hydrophobic peptides and possibly membrane proteins.