High-Resolution Ion Mobility-Based Isotopic Shifts of Dimethylated Peptide Isomers

Area of Science:

• Analytical Chemistry
• Biochemistry
• Structural Biology

Background:

• Peptide and protein isomerization impacts biological function.
• Existing Ion Mobility Spectrometry-Mass Spectrometry (IMS-MS) methods offer limited structural insights.
• Distinguishing peptide isomers is crucial for understanding biological processes.

Purpose of the Study:

• To investigate isotopic dimethylation for generating isomer-specific isotopic shifts.
• To assess the utility of these shifts in high-resolution cyclic ion mobility separations.
• To complement existing IMS-MS techniques for peptide isomer characterization.

Main Methods:

• Utilized isotopic dimethylation to label peptide isomers.
• Employed high-resolution cyclic ion mobility separations to measure arrival time differences.
• Applied molecular modeling to understand the origins of observed shifts.

Main Results:

• Observed isomer-specific arrival time shifts diagnostic for lysine and beta-amyloid isomers.
• Shift magnitude and direction varied systematically with peptide sequence.
• Isotopic shifts provided information orthogonal to conventional IMS-MS, linked to mass distribution changes.

Conclusions:

• Isotopic dimethylation-based shifts are a broadly applicable tool for peptide isomer characterization.
• This method offers a structurally sensitive dimension to IMS-MS.
• The approach reveals isomer-dependent changes in center of mass and moments of inertia.