Synthesis and conformational analysis of macrocyclic peptides consisting of both [alpha]-helix and polyproline helix segments

Macrocycles are interesting molecules because their topological features and constrained properties significantly affect their chemical, physical, biological, and self-assembling properties. In this report, we synthesized unique macrocyclic peptides composed of both an [alpha]-helix and a polyproline segment and analyzed their conformational properties. We found that the molecular stiffness of the rod-like polyproline segment and the relative orientation of the two different helical segments strongly affect the efficiency of the macrocyclization reaction. Conformational analyses showed that both the [alpha]-helix and the polyproline II helix coexisted within the macrocyclic peptides and that the polyproline segment exerts significant effect on the overall helical stability and conformation of the [alpha]-helical segment. copyright 2013 Wiley Periodicals, Inc. Biopolymers 101: 279-286, 2014.