Structural Mimicry of Two Cytochrome b_(562) Interhelical Loops Using Macrocycles Constrained by Oxazoles and Thiazoles

摘要

A major chemical challenge is the structural mimicry of discontinuous protein surfaces brought into close proximity through polypeptide folding. We report the design, synthesis, and solution structure of a highly functionalized saddle-shaped macrocyclic scaffold, constrained by oxazoles and thiazoles, supporting two short peptide loops projecting orthogonally from the same face of the scaffold. This structural mimetic of two interhelical loops of cytochrome b_(562) illustrates a promising approach to structurally mimicking discontinuous loops of proteins.