π-Helix Preference in Unsolvated Peptides

Abstract

Ion mobility measurements have been used to examine helix formations in the gas phase for a series of alanine/glycine-based peptides that incorporate a glutamic acid (E) and lysine (K) at various positions along the backbone. Incorporation of an EK pair lowers the percent helix for all positions (presumably because hydrogen bonding between the backbone and the E and K side chains stabilize the nonhelical globular conformations). The largest percent helix is found when the EK pair is in an i,i+5 arrangement, which suggests that the preferred helical conformation for these peptides is a pi-helix. This conclusion is supported by comparison of cross sections deduced from the ion-mobility measurements to average cross sections calculated for conformations obtained from molecular dynamics simulations. The glutamic acid and lysine may form an ion pair that is stabilized by interactions with the helix macro-dipole.

Factors That Influence Helical Preferences for Singly Charged Gas-Phase Peptide Ions: The Effects of Multiple Potential Charge-Carrying Sites

“…The structures contained in Figure 2 focus on a single type of interaction, charge solvation of the protonated ε-amino group of lysine; however, ion-pairing (salt-bridge type interactions) between the E and K groups also accounts for significant proportion of the globular structural population. This conclusion is consistent with Jarrold’s previous results which showed that insertion of an E/K pair into Ac-A 3 G 12 K in the i, i+3 spacing decreased helix abundance with respect to globular structures;53 the authors suggested that the main reason for decreased helical content was competition for backbone H-bonds by side-chains, resulting in destabilization of the helix. Likewise, this conclusion is also supported by the IR-UV double resonance spectral features for Ac-Phe-(Ala) 10 -LysH + versus that for Ac-Lys(H + )-Phe-(Ala) 10 , which are helical and globular, respectively 20.…”

Trapping a Folding Intermediate of the α-Helix: Stabilization of the π-Helix

“…We employed several means to explore the stability of HBS π-helices. The observation that switching of a single potential i-i + 5 salt bridge in 3 to an i-i + 4 salt bridge (HBS 2) leads to a mixture of at least two interconverting conformations suggests the stabilizing role of appropriately placed side chain interactions (8,38). We conjecture that the second conformation in 2 corresponds to an R-helical structure stabilized by the i-i + 4 salt bridge, as the π-helix has been proposed as an intermediate in the unfolding of R-helices (6,9,14).…”

Ion mobility–mass spectrometry

“…Effects of water on unfolding and refolding in the gas phase can be monitored with IMMS 143. In addition, ion mobility can be used to determine the effect of d‐residues on helix formation 144…”