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

Award Number: R35GM153191
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $365,948 )
2025	2025	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE # 1100	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	001	2	4/9/2025	NON-COMPETING CONTINUATION	$365,948
2025	2024	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE # 1100	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	000	1	11/21/2024	NEW	$0
														Subtotal = $365,948

Issue Date FY: 2024 ( Subtotal = $365,948 )
2024	2024	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE # 1100	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	000	1	4/19/2024	NEW	$365,948
														Subtotal = $365,948

Grand Total All Awards = $731,896

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

Award Number: R35GM153191

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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