Synthesis and Conformational Analysis of Macrocyclic Peptides Consisting of Both α-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 -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 -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 -helical segment. (c) 2013 Wiley Periodicals, Inc. Biopolymers 101: 279-286, 2014.