Methods of Glycosylation and Bioconjugation
Background:
The National Cancer Institute's
Structural Glycobiology Laboratory is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, and/or commercialize methods
of glycosylation and bioconjugation that can be used to regulate
cellular recognition and interaction.
Technology:
Eukaryotic cells express several
classes of oligosaccharides attached to proteins or lipids. Animal
glycans can be N-linked via B-GlcNAc to Asn (N-glycans), O-linked
via -GalNAc to Ser/Thr (O-glycans), or can connect the carboxyl end
of a protein to a phosphatidylinositol unit (GPI-anchors) via a
common core glycan structure. Beta (1,4)-galactosyltransferase I
catalyzes the transfer of galactose from the donor, UDP-galactose,
to an acceptor, N-acetylglucosamine, to form a galactose-beta
(1,4)-N-acetylglucosamine bond, and allows galactose to be linked
to an N-acetylglucosamine that may itself be linked to a variety of
other molecules. Examples of these molecules include other sugars
and proteins. The reaction can be used to make many types of
molecules having great biological significance. For example,
galactose-beta (1,4)-N-acetylglucosamine linkages are important for
many recognition events that control how cells interact with each
other in the body, and how cells interact with pathogens. In
addition, numerous other linkages of this type are also very
important for cellular recognition and binding events as well as
cellular interactions with pathogens, such as viruses. Therefore,
methods to synthesize these types of bonds have many applications
in research and medicine to develop pharmaceutical agents and
improved vaccines that can be used to treat disease.
The invention provides in vitro folding method for a
polypeptidyl-a-N-acetylgalactosaminyltransferase (pp-GalNAc-T) that
transfers GalNAc to Ser/Thr residue on a protein. The application
claims that this in vitro-folded recombinant ppGalNAc-T enzyme
transfers modified sugar with a chemical handle to a specific site
in the designed C-terminal polypeptide tag fused to a
protein.
Further R&D
Needed:
- Development of a targeted drug delivery system.
- Attachment of fluoroprobes or imaging agents to proteins
R&D Status:
Enzymes have been synthesized and characterization studies have
been performed.
IP Status:
U.S. Provisional Application No. 60/930,294
Value Proposition:
- Methods for engineering a glycoprotein from a biological
substrate, and methods for glycosylating a biological substrate for
use in glycoconjugation;
- Enzymes and methods that can be used to promote the chemical
linkage of biologically important molecules that have previously
been difficult to link;
- Diagnostics and therapeutics utilizing these methods.
Contact
Information:
John D. Hewes, Ph.D., NCI
Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov
Reference: #598 JH
Posted 12/26/2007
This opportunity is also listed under the following categories: