title: Toward a Rational Design of Highly Folded Peptide Cation Conformations. 3D Gas-Phase Ion Structures and Ion Mobility Characterization.
abstract: Heptapeptide ions containing combinations of polar Lys, Arg, and Asp residues with non-polar Leu, Pro, Ala, and Gly residues were designed to study polar effects on gas-phase ion conformations. Doubly and triply charged ions were studied by ion mobility mass spectrometry and electron structure theory using correlated ab initio and density functional theory methods and found to exhibit tightly folded 3D structures in the gas phase. Manipulation of the basic residue positions in LKGPADR, LRGPADK, KLGPADR, and RLGPADK resulted in only minor changes in the ion collision cross sections in helium. Replacement of the Pro residue with Leu resulted in only marginally larger collision cross sections for the doubly and triply charged ions. Disruption of zwitterionic interactions in doubly charged ions was performed by converting the C-terminal and Asp carboxyl groups to methyl esters. This resulted in very minor changes in the collision cross sections of doubly charged ions and even slightly diminished collision cross sections in most triply charged ions. The experimental collision cross sections were related to those calculated for structures of lowest free energy ion conformers that were obtained by extensive search of the conformational space and fully optimized by density functional theory calculations. The predominant factors that affected ion structures and collision cross sections were due to attractive hydrogen bonding interactions and internal solvation of the charged groups that overcompensated their Coulomb repulsion. Structure features typically assigned to the Pro residue and zwitterionic COO-charged group interactions were only secondary in affecting the structures and collision cross sections of these gas-phase peptide ions. Graphical Abstract ᅟ.
authors.affiliation: Department of Chemistry, Bagley Hall, University of Washington, Seattle, WA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Pepin
authors.affiliation: Department of Chemistry, Bagley Hall, University of Washington, Seattle, WA, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Laszlo
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Aleš
authors.initials: A
authors.lastname: Marek
authors.affiliation: Department of Chemistry, Bagley Hall, University of Washington, Seattle, WA, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.affiliation: Department of Chemistry, Bagley Hall, University of Washington, Seattle, WA, USA.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Bush
authors.affiliation: Laboratoire COBRA CNRS UMR 6014 & FR 3038, Université de Rouen, INSA de Rouen, Mont St Aignan Cedex, France.
authors.forename: Helène
authors.initials: H
authors.lastname: Lavanant
authors.affiliation: Laboratoire COBRA CNRS UMR 6014 & FR 3038, Université de Rouen, INSA de Rouen, Mont St Aignan Cedex, France.
authors.forename: Carlos
authors.initials: C
authors.lastname: Afonso
authors.affiliation: Department of Chemistry, Bagley Hall, University of Washington, Seattle, WA, USA. turecek@chem.washington.edu.
authors.forename: František
authors.initials: F
authors.lastname: Tureček
mesh_terms: D002412:Cations; D006371:Helium; D000075663:Ion Mobility Spectrometry; D010455:Peptides; D011487:Protein Conformation
chemical_list: D002412:Cations; D010455:Peptides; D006371:Helium
keywords: Collisional cross sections; Density functional theory calculations; Ion mobility; Ion structures; Peptide ions; Polar effects