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Integrated tools for higher order structure determination by cross link analysis

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41GM122169-01A1
Agency Tracking Number: R41GM122169
Amount: $224,870.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 100
Solicitation Number: PA16-303
Timeline
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-09-01
Award End Date (Contract End Date): 2019-02-28
Small Business Information
1622 SAN CARLOS AVE, SUITE C
San Carlos, CA 94070-2060
United States
DUNS: 967100921
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 BEATRIX UEBERHEIDE
 (212) 263-2546
 beatrix.ueberheide@nyumc.org
Business Contact
 CHRISTOPHER BECKER
Phone: (650) 412-4210
Email: becker@proteinmetrics.com
Research Institution
 NYU WINTHROP HOSPITAL
 
259 1ST ST
MINEOLA, NY 11501-3957
United States

 Domestic Nonprofit Research Organization
Abstract

Summary
The use of mass spectrometry MS for quantitative protein characterization has increased
dramatically identifying and quantifying thousands of proteins is no longer a heroic task nor is
characterizing therapeutic proteins in detail Due to widely available software quantitative mass
spectrometry has become routine and widely used for addressing questions in basic biology
translational medicine and drug development MS Methods are now poised to have similar
impact on the study of protein protein interaction and higher order structure HOS
determination
In particular crosslinking mass spectrometry which obtains distance and accessibility
constraints from two ended chemical modifications is emerging as a powerful tool to map
protein protein interaction interfaces Recent years have seen large improvements in crosslink
mass spectrometry Yet despite these advances crosslink analysis is not yet a technique that
has found widespread use due to a range of problems such as the low abundance of
crosslinked peptides unavailability of proprietary reagents the need for different search
algorithms adopted to specific cross linkers and the difficulty of reliably characterizing
crosslinked peptide spectra
To alleviate these problems and democratize the use of crosslinking we propose to develop
standardized and effective methods for crosslinking in conjunction with sensitive and accurate
search algorithms incorporated into our well established Byonic search engine Our algorithms
will support almost all commercially available crosslinking chemistries and most major peptide
fragmentation methods ETD CAD HCD EthcD as well as cleavable and non cleavable
crosslinkers The near universal applicability and ease of use of the software will promote rapid
adoption of crosslinking mass spectrometry in academic research and biopharmaceutical
development Narrative

We propose to develop methods and commercial software products for easy determination of the
structure and interactions of biologically important proteins The proposed project has the potential for
great impact on human health in areas such as medical research drug and vaccine development and
therapeutic protein characterization

* Information listed above is at the time of submission. *

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