Description of Invention:
Glycans can be classified as linear or branched sugars. The linear sugars are the glycosaminoglycans comprising polymers of sulfated disaccharide repeat units that are O-linked to a core protein, forming a proteoglycan aggregate. The branched glycans are found as N-linked and O-linked sugars on glycoproteins or on glycolipids. These carbohydrate moieties of the linear and branched glycans are synthesized by a super family of enzymes, the glycosyltransferases (GTs), which transfer a sugar moiety from a sugar donor to an acceptor molecule. Although GTs catalyze chemically similar reactions in which a monosaccharide is transferred from an activated derivative, such as a UDP-sugar, to an acceptor, very few GTs bear similarity in primary structure.
Eukaryotic cells express several classes of oligosaccharides attached to proteins or lipids. Animal glycans can be N-linked via beta-GlcNAc to Asparagine (N-glycans), O-linked via UDP-GalNAc to Serine/Threonine (O-glycans), or can connect the carboxyl end of a protein to a phosphatidylinositol unit (GPI-anchors) via a common core glycan structure. Thus, there is potential to develop carbohydrate substrates comprising bioactive agents that can be used to produce glycoconjugates carrying sugar moieties with bioactive agents. Such glycoconjugates have many therapeutic and diagnostic uses, e.g. in labeling or targeted delivery. Further, such glycoconjugates can be used in the assembly of bio-nanoparticles to develop targeted-drug delivery systems or contrast agents for medical uses.
This application claims methods and compositions for making and using functionalized sugars. Also claimed in the application are methods for forming a wide variety of products at a cell or in an in vitro environment. More specifically, the claimed compositions of the invention comprise a sugar nucleotide and one or more functional groups.
Applications:
Production of therapeutic or diagnostic glycoconjugates, assembly of bio-nanoparticles, development of contrast agents.
Development Status:
Enzymes have been synthesized and initial studies have been performed.
Patent Status:
DHHS Reference No. E-016-2008/0 --
U.S. Provisional Application No. 61/027,782 filed 11 Feb 2008
Relevant Publication:
B Ramakrishnan et al. Applications of glycosyltransferases in the site-specific conjugation of biomolecules and the development of a targeted drug delivery system and contrast agents for MRI. Expert Opin Drug Deliv. 2008 Feb;5(2):149-153. Review. [PubMed abs]
PK Qasba et al. Site-specific linking of biomolecules via glycan residues using glycosyltransferases. Biotechnol Prog. 2008 May-Jun;24(3):520-526. [PubMed abs]
Licensing Status: Available for exclusive or non-exclusive licensing.
Collaborative Research Opportunity:
The National Cancer Institute’s Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the synthesis of UDP derivatives of C2 modified galactose for use as donor substrates for glycosyltransferases. Please contact John D. Hewes, Ph.D. at 301-435-3121 or < a href="mailto:hewesj@mail.nih.gov">hewesj@mail.nih.gov for more information.
For Additional Information Please Contact: Peter A. Soukas J.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-4646
Email: soukasp@mail.nih.gov
Fax: (301) 402-0220
