Semi-synthesis of interleukin-1α via expressed threonine ligation and native chemical ligation-desulfurization

IL-1α is a pleiotropic cytokine that is involved in various immune responses, such as inflammatory processes and hematopoiesis. Herein, we report the semi-synthesis of Interleukin-1α by expressed threonine ligation and native chemical ligation-desulfurization. This method involves two critical steps: 1) The ligation between the peptide containing a C-terminal salicylaldehyde ester and the peptide possessing an N-terminal Thr residue, and 2) the ligation between the peptide containing a C-terminal thioester and the peptide possessing an N-terminal β-thiolated leucine. The applicability of this methodology can also be introduced into the synthesis of other Cys-free glycoproteins.