Amidine Functionality As a Conformational Probe of Cyclic Peptides.

The amidine functionality switches between hydrogen bond donor and acceptor roles depending on pH. Herein, the amidine was incorporated to select amides in cyclo(d-Ala-Pro-d-Phe-Pro-Gly). The unprotonated amidine-containing macrocyclic conformation resembles its oxoamide counterpart. Upon protonation, minimal alterations in the macrocyclic conformation were observed despite changes to the hydrogen bond network. The amidine disrupts hydrogen bonding at minimal steric cost, making it a useful functionality to study the effect of hydrogen bonding on the macrocyclic conformation.