Modular Assembly of Macrocyclic Organo–Peptide Hybrids Using Synthetic and Genetically Encoded Precursors

Mix, click, cyclize: Conformationally constrained organo–peptide hybrids can be constructed by a tandem chemoselective reaction between a synthetic molecule and a recombinant protein. Diverse macrocyclic structures were obtained in cyclic, lariat, and protein-tethered configurations by varying the nature of the synthetic and biosynthetic precursors.