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

This 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. 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.