Improved Glycoinformatics Tools for the Interpretation of Sequential Mass Spectra

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43RR025988-01
Agency Tracking Number: RR025988
Amount: $120,000.00
Phase: Phase I
Program: SBIR
Awards Year: 2009
Solicitation Year: 2009
Solicitation Topic Code: N/A
Solicitation Number: PHS2009-2
Small Business Information
DUNS: 018796322
HUBZone Owned: Y
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 () -
Business Contact
Phone: (603) 553-6697
Research Institution
DESCRIPTION (provided by applicant): Glycans (carbohydrates) can covalently attach to, and affect the function of, proteins and lipids. Understanding and modifying the glycan components of a glycoprotein are key steps toward the development and refinement of many therapeutic drugs. Glycans are also significant in a number of biological and biomedical research areas. For instance, glycans are biomarkers for various cancers, the principal component of new and promising vaccines, and drive parasite-host and microbe-host interactions, as well as egg fertilization, protein folding, and more. Defective glycan assembly or metabolism manifests itself as Congenital Disorders of Glycosylation, Gaucher, Fabry, Tay-Sachs, and Sandhoff diseases, among others. Research in these and related areas is hindered by the lack of effective glycan sequencing tools and methods. Currently, there are no commercially-available comprehensive analytical strategies to determine glycan structures. Glycome Technologies Inc. (GT) is a newly-formed commercial venture whose goal is to provide glycoanalytic services to pharmaceutical companies. To assist in performing these analyses, we are developing a series of proprietary glycoinformatics tools to enable efficient glycan analysis via sequential mass spectrometry (MSn). This collection of tools is known as gtSuite(tm). GT is requesting funding to support the development of two software components: (1) gtAnnotate(tm), used for MSn spectrum annotation and viewing, and (2) gtIsoDetect(tm), used to detect the presence of structural isomers (glycans which contain the same monosaccharide residues, but linked in different ways to form distinct structures). Analysis of glycan structures via MSn is a currently labor-intensive task suitable only for experts. However, bolstered by the enhanced capabilities of a mature gtSuite, Glycome Technologies will be able to offer cost-effective glycoanalytic services, including detailed glycan structural analysis and monitoring of the batch-to-batch glycosylation patterns of glycoprotein therapeutics. PUBLIC HEALTH RELEVANCE: The enhanced glycan analysis capabilities afforded by a mature gtSuite(tm) glycoinformatics platform will accelerate the pace of glycoprotein therapeutic development (Dove 14; Koeller and Wong 45; Walsh 84). It will also provide insights into a number of biological and biomedical research areas where glycans play a significant role, including cancer biomarker discovery (Alper 2; Dziadek and Kunz 17; Ono and Hakomori 59; Turner 76); vaccine discovery (Ada and Isaacs 1; Dwek 16; Gaucher 22; Lo- Man 53; Muhlecker 57); parasite-host and microbe-host interactions (Hokke and Deedler 36; Khoo and Dell 44; Nyame 58); and diseases such as Congenital Disorders of Glycosylation, Gaucher, Fabry, Tay-Sachs, and Sandhoff (Butters 8; Dwek 16; Jaeken and Matthijs 40; Jeyakumar 41; Platt 61; Vosseller 82). Research in these and related areas is hindered by the lack of effective glycan sequencing tools and methods (Stephan 73), and will benefit from the software proposed here.

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

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