Metal-Binding Q-Proline Macrocycles

Abstract

We introduce the efficient Fmoc-SPPS and peptoid synthesis of Q-proline-based, metal-binding macrocycles (QPMs), which bind metal cations and display nine functional groups. Metal-free QPMs are disordered, evidenced by NMR and a crystal structure of QPM-3 obtained through racemic crystallization. Upon addition of metal cations, QPMs adopt ordered structures. Notably, the addition of a second functional group at the hydantoin amide position (R₂) converts the proline ring from Cγ-endo to Cγ-exo, due to steric interactions.