Novel Materials and Methods for Separations of Glycopeptides and Glycans

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 2R44GM093747-02
Agency Tracking Number: R44GM093747
Amount: $1,161,877.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: NIGMS
Solicitation Number: PA11-215
Solicitation Year: 2013
Award Year: 2013
Award Start Date (Proposal Award Date): 2013-08-01
Award End Date (Contract End Date): 2016-11-30
Small Business Information
3521 SILVERSIDE ROAD, SUITE 1-K, QUILLEN BLDG, Wilmington, DE, 19810-4900
DUNS: 557435273
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (302) 981-0583
Business Contact
Phone: (302) 477-2513
Research Institution

DESCRIPTION provided by applicant Analysis of glycoprotein polypeptide sites of carbohydrate attachment and the structures of the glycans present on these proteins requires the combination of high resolution chromatographic separations and sophisticated mass spectrometry Hydrophilic interaction liquid chromatography HILIC has great use in separations of glycopeptides and released glycans exhibiting remarkable selectivity for the separations of glycoforms The proposed effort is to markedly improve separations of glycopeptides and released glycans by HILIC reducing the separation times from the current hours per sample to minutes or less The separations component of LC MS analysis of glycoproteins can benefit from the design of more efficient stationary phase chromatographic materials and from the use of conditions that allow direct and productive interfacing with mass spectrometers We propose that recently developed superficially porous silica microparticulate silica packing materials Fused Core R structures can achieve these separation speeds without loss of the required high resolution The AMT Fused Core reversed phase materials have previously been shown to exhibit superior kinetic properties and column efficiencies for separations of small molecules and recently wider pore size packings have shown a similar benefit for larger peptides c kDa The current proposal uses Fused Core technology with unique surface modifications to develop high performance HILIC materials specifically for separations of glycopeptides and glycans Tailored HILIC materials will be synthesized and tested for HILIC operation as well as to establish the fundamental relationships between surface properties particle characteristics and utility for glycan and glycopeptides separations The new bonded phases utilize organosilane chemistry discovered in Phase I efforts that have been selected to withstand aggressive conditions of use permitting stable and robust separations materials that can be used across a broad range of conditions Preliminary LC MS applications in glycoproteomic applications have been completed in Phase A reasonable estimate is that an improvement of andgt fold for separations times are obtained Phase II will expand on this effort with the purpose of delivering further improved materials and methods to a broader range of needs in glycoproteomics and proteomics workflows A significant aspect of the current proposal will assess the benefits and real world applications of these new separations materials The target of this work is to produce robust materials that permit simple integration with online mass spectrometry analysis effective for resolution of the complex mixtures that are typical of current glycoprotein identification and structural characterization procedures PUBLIC HEALTH RELEVANCE Protein modification by the addition of sugars called glycosylation is extremely common in nature and this modification exhibits a strong effect on protein structure and on biological function In certain diseases most notably in cancer and for some infectious diseases like influenza glycosylation of proteins or recognition of such proteins is altered in ways that are not fully understood In some cases these alterations are big enough to allow them to be used for recognition of disease and in some cases to stratify patients The current proposal is to use new knowledge in materials science and chemistry to enable much faster and more efficient ways to discover glycosylation disease markers and to better understand the biology of glycosylation

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

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