Solution-Phase Automated Synthesis of Oligosaccharides

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$190,341.00
Award Year:
2010
Program:
STTR
Phase:
Phase I
Contract:
1R41GM088888-01A1
Agency Tracking Number:
R41GM088888
Solicitation Year:
2010
Solicitation Topic Code:
NIGMS
Solicitation Number:
PHS2010-2
Small Business Information
IOWA STATE UNIVERSITY
1030 ROY J CARVER CO-LABORATORY, AMES, IA, 50011-
Hubzone Owned:
N
Socially and Economically Disadvantaged:
N
Woman Owned:
Y
Duns:
827100350
Principal Investigator:
NICOLA POHL
(515) 294-2339
NPOHL@IASTATE.EDU
Business Contact:
BEATRICE MARIE
(515) 294-5225
egrants@iastate.edu
Research Institution:
Iowa State University

1138 PEARSON HALL
AMES, IA, 50011-2207
() -
Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): The synthesis of carbohydrates remains a complex exercise that involves tremendous labor and large amounts of expensive building blocks and reagents. Even once a process for making a carbohydrate has been developed, manufacture of that molecule in all the variants that biologists demand for their studies to drive glycomics remains labor and material intensive. The lack of ready access to a range of carbohydrate structures, given the extreme difficulty in isolating sufficient and pure quantities from natural sources, has been a severe limitation to advancing not only the science but also the resulting carbohydrate based vaccines and diagnostics built on this basic understanding. The long-term goal of the proposed project is to develop the commercial custom synthesis of oligosaccharides using stable and, if possible, crystalline building blocks in association with an innovative new automated solution-phase process for building block assembly. This phase I proposal addresses roadblocks that stand in the way of the development of this process at this stage. The specific aims are 1) the preparation of a range of N-phenyl substituted trifluoroacetimidoyl halides as glycosyl activating reagents; 2) the preparation of different trifluoroacetimidoyl based glycosyl donors with tests of their stability and reactivity; and 3) the reaction of these donors with a range of glycosyl acceptors to form disaccharide libraries in a solution-phase-based automation strategy amenable to iterative oligosaccharide synthesis. At the conclusion of these studies, stable glycosyl donors reactive with a wide range of glycosyl acceptors in a solution phase automation platform will have been discovered to pave the way for a standardized set of carbohydrate building blocks for on-demand custom-order oligosaccharide synthesis. PUBLIC HEALTH RELEVANCE: Carbohydrates are increasingly recognized as fundamental molecular constituents in a wide range of cellular processes of medical importance, including infectious disease responses (fungal, e.g candidiasis; viral, e.g. influenza; and bacterial, e.g. Staphylococcus aureus), cancer progression, and congenital metabolic disorders (e.g. mucopolysaccharidosis). This proposal will develop methods for the first rapid automated assembly of oligosaccharides in solution for use in medical diagnostics and basic science studies.

* information listed above is at the time of submission.

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