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.
Bibliographical noteFunding Information:
This work was supported by National Institutes of Health Research Grant R01-GM090323 (J.A.C.) and NIH Grant 5R01GM085006-02 (A.S.); and by the Department of Defense Congressionally Directed Medical Research Program Grant PC09305 (J.A.C.).
- Antimicrobial peptide
- Cyclic peptide