Peptide Conformational Determination With Vibrational Circular Dichroism and Isotope Labeling: Focused Review of 3 ₁₀ ‐Helical Peptide Spectroscopic Structural Studies

Optical spectroscopic techniques have long been used to determine average secondary structure in proteins and peptides, but these are primarily limited to determination of relative sheet and helix content, with the remainder often designated as “other.” Several decades ago, in cooperation with Claudio Toniolo and co‐workers, our group at UIC was able to show that vibrational circular dichroism (VCD) could be used to distinguish between formation of 3 10 ‐helices and α‐helices in small peptides, as well as from other uniform structures. Conventional electronic CD (ECD) or infrared (IR) spectroscopy did not give unambiguous distinctions between these two right‐handed, internally H‐bonded, helical forms. Theoretical modeling of the VCD spectra showed that the differences between helical forms could not be attributed to just use of Aib residues or of organic solvents, both used to stabilize the 3 10 conformation. Later we showed that, with IR and VCD enhanced by isotopic labeling, it was possible to differentiate site‐specific structures using vibrational spectra interpreted with DFT‐level theoretical modeling. These advances are briefly reviewed here and results of applying them to 3 10 ‐helical structures are discussed.