Head-to-tail cyclization of side chain-protected linear peptides to recapitulate genetically-encoded cyclized peptides.

ABSTRACT: Genetically-encoded cyclic peptide libraries allow rapid in vivo screens for inhibitors of any target protein of interest. In particular, the Split Intein Circular Ligation of Protein and Peptides (SICLOPPS) system exploits spontaneous protein splicing of inteins to produce intracellular cyclic peptides. A previous SICLOPPS screen against Aurora B kinase, which plays a critical role during chromosome segregation, identified several candidate inhibitors that we sought to recapitulate by chemical synthesis. We describe the syntheses of cyclic peptide hits and analogs via solution-phase macrocyclization of side chain-protected linear peptides obtained from standard solid-phase peptide synthesis. Cyclic peptide targets, including cyclo-[CTWAR], were designed to match both the variable p

SUBMITTER: Bouayad-Gervais S 

PROVIDER: S-EPMC9286623 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature