High-specificity affinity reagents for N-glycosylation site mapping and glycomics

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$200,361.00
Award Year:
2009
Program:
STTR
Phase:
Phase I
Contract:
1R41GM086991-01A1
Award Id:
93821
Agency Tracking Number:
GM086991
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
GLYCOSENSORS AND DIAGNOSTICS, LLC, 250 GREYSTONE TER, ATHENS, GA, 30606
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
808436633
Principal Investigator:
ROBERT WOODS
(706) 542-4454
RWOODS@CCRC.UGA.EDU
Business Contact:
ROBERT WOODS
() -
glycosensors@gmail.com
Research Institute:
UNIVERSITY OF GEORGIA (UGA)

UNIVERSITY OF GEORGIA
Office of Sponsored Programs
ATHENS, GA, 30602 7411

Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): Glycans have several distinct properties that make them excellent targets for disease biomarkers. Firstly, the location of the glycans on the cell surface makes them the first point of contact of cellular interactions a nd thus crucial in the control of normal metabolic processes. Cell surface molecules are also strategically exposed for surveillance by the immune system allowing for the potential of immune recognition of abnormal cells. Secondly, specific glycan structur es that are not present, or are in low amounts, in normal states proliferate in disease states. And lastly, changes in glycosylation involve many proteins, including those that are highly abundant. Therefore, a single change in a cell's glycosylation machi nery can affect many different glycoconjugates. To effectively employ and discover glycan disease markers new glycan-specific reagents are urgently needed. Using structurally guided genetic manipulations, we will convert the PNGase F carbohydrate-processin g enzyme into a high-specificity affinity reagent for peptides and proteins that contain asparagine-linked carbohydrate chains. Because such a protein has lectin-like properties, but is derived from an enzyme, we are calling them LectenzTM . Lectenz have several potential advantages over lectins and antibodies, including precise definition of specificity, ease of preparation in a monovalent form, and (for human homologues) minimal in vivo toxicity. The PNGase F lectenz may be employed directly to address t he needs of glycomics/proteomics analysis through sample enrichment, thus facilitating glycosylation site-mapping. Glycosylation site mapping is currently extremely tedious to perform and yet is essential in fully characterizing and exploiting glycans as m arkers of specific disease states. The principle advantages of an engineered lectenz over an antibody are that the lectenz is specific to the carbohydrate sequence, but, in contrast to antibodies, will recognize that sequence in a broad range of glycans. F urther, in contrast to plant lectins, engineered lectenz are derived from enzymes that have exquisite substrate specificities and low toxicities. PUBLIC HEALTH RELEVANCE: Using structurally-guided genetic manipulations we will convert the PNGase F carbohyd rate-processing enzyme into a high-specificity affinity reagent (called a LectenzTM) for peptides and proteins that contain asparagine-linked carbohydrate chains. The principle advantages of engineered lectenz over other reagents, such as antibodies or lec tins, is that they have exquisite sequence specificity that is not context dependent, they have well defined substrate specificity, and they may be produced as monomeric proteins.

* information listed above is at the time of submission.

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