# Novel Ion Chemistry and Instrument Development for the Characterization of Proteins, Nucleic Acids, and Heterogeneous Bio-complexes via Tandem Mass Spectrometry

> **NIH NIH R35** · PURDUE UNIVERSITY · 2024 · $365,948

## Abstract

Project Summary
Mass spectrometry and tandem mass spectrometry have become essential tools in virtually all of the molecular
sciences associated with biomedical research. Many questions of interest can be addressed by breaking
macromolecules of interest (e.g., proteins) into smaller fragments prior to analysis. However, information
inherently present in intact macromolecules and their complexes is lost upon digestion, which has motivated the
development of so-called “top-down proteomics” and “native mass spectrometry”. While major advances have
been made in both of these areas, significant challenges remain, particularly for high mass heterogenous
mixtures. This effort emphasizes novel ion chemistries and novel instrumentation directed to challenges in top-
down tandem mass spectrometry of biopolymers and their complexes. Particular emphasis is placed on the
attachment of multiply-charged ions to high-mass analyte ions of opposite polarity to facilitate mass
measurement, mixture analysis, and structural characterization. The controlled attachment of reagents of known
mass and charge can dramatically improve the ‘peak capacity’ of a mass spectrometry measurement applied to
complex mixtures of ions derived from electrospray ionization. Furthermore, ion attachment, in conjunction with
MSn workflows, may prove to be useful in revealing the surface exposure of components in a complex. Novel
ion/ion reactions involving superacid anions may also prove to be useful as gas-phase means for the selective
removal of metal ions that become incorporated in bio-complexes ionized under native conditions. This effort
also involves instrument development aimed at supporting high mass-to-charge ion manipulation (e.g., digital
ion trap operation for ion isolation and ion parking of high mass-to-charge ions) and measurement (digital ion
trap operation and electrostatic ion trap mass analysis) to support multiply-charged ion attachment experiments.
The effort will extend the utility of mass spectrometry and tandem mass spectrometry in top-down biopolymer
characterization as well as in the mass measurement and characterization of large complexes, such as molecular
machines and viruses.

## Key facts

- **NIH application ID:** 10838861
- **Project number:** 1R35GM153191-01
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** SCOTT A MCLUCKEY
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $365,948
- **Award type:** 1
- **Project period:** 2024-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10838861

## Citation

> US National Institutes of Health, RePORTER application 10838861, Novel Ion Chemistry and Instrument Development for the Characterization of Proteins, Nucleic Acids, and Heterogeneous Bio-complexes via Tandem Mass Spectrometry (1R35GM153191-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10838861. Licensed CC0.

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