title: Multiple gas-phase conformations of proline-containing peptides: is it always cis/trans isomerization?
abstract: Ion mobility-mass spectrometry (IM-MS) is often employed to look at the secondary, tertiary, and quaternary structures of naked peptides and proteins in the gas-phase. Recently, it has offered a unique glimpse into proline-containing peptides and their cis/trans Xxx-Pro isomers. An experimental "signature" has been identified wherein a proline-containing peptide has its Pro residues substituted with another amino acid and the presence or absence of conformations in the IM-MS spectra is observed. Despite the high probability that one could attribute these conformations to cis/trans isomers, it is also possible that cis/trans isomers are not the cause of the additional conformations in proline-containing peptides. However, the experimental evidence of such a system has not been demonstrated or reported. Herein, we present the IM-MS analysis of Neuropeptide Y's wild-type (WT) signal sequence and Leu7Pro (L7P) mutant. Although comparison of arrival times and collision cross-sections of [M + 4H](4+) ions yields the cis/trans "signature", molecular dynamics indicates that a cis-Pro7 is not very stable and that trans-Pro7 conformations of the same cross-section arise with equal frequency. We believe that this work further underscores the importance of theoretical calculations in IM-MS structural assignments.
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA. lingjun.li@wisc.edu.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Lietz
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA. lingjun.li@wisc.edu.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA. lingjun.li@wisc.edu.
authors.forename: Chang
authors.initials: C
authors.lastname: Yun Son
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA. lingjun.li@wisc.edu.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA. lingjun.li@wisc.edu and School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Li