Efficient one-pot cyclization/folding of Rhesus θ-defensin-1 (RTD-1)

We report an efficient approach for the chemical synthesis of Rhesus θ-defensin-1 (RTD-1) using Fmoc-based solid-phase peptide synthesis in combination with an intramolecular version of native chemical ligation. The corresponding linear thioester precursor was cyclized and folded in a one-pot reaction using reduced glutathione. The reaction was extremely efficiently yielding natively folded RTD-1 with minimal or no purification at all. This approach is fully compatible with the high throughput production of chemical libraries using this peptide scaffold.

Graphical abstractThis communication describes an efficient synthesis of Rhesus θ-defensin-1 (RTD-1) using optimized Fmoc-based solid-phase synthesis in combination with an one-pot GSH-induced cyclization and folding reaction. The high efficiency of this approach makes it suitable for the production of chemical libraries using RTD-1 as molecular scaffold.Figure optionsDownload full-size imageDownload as PowerPoint slide