Macrocyclic peptide construction through C-H activation strategy

Peptides are biomolecules that commonly engage in biological activities of native bio-systems, and have also been inspiringly investigated, synthesized and utilized by human beings for clinical purposes. The function of a peptide is typically dependent on its amino acid sequence and three-dimensional structure. Among all types of peptides, macrocyclic ones that confer well-defined conformations and extended surface, and thus lead to enhanced thermo/metabolic stability and cell permeability, have emerged as highly promising candidates in therapeutic development, as exemplified by Vancomycin antibiotics [1]. To construct such peptidic macrocycles, nature has demonstrated privileged machineries by employing a set of different enzymes to assemble all fragments. However, such biosynthetic scenarios are very limited to those natively found products and difficult to be extended to designed macrocyclic peptides, which prompts chemists to develop synthetic methods to expand their structural diversity and also explore their potential biological applications