Alpha 1-3 N-Acetylgalactosaminyltransferases with Altered Donor and Acceptor Specificities, Compositions, and Methods of Use
Description of Invention:
The present invention relates to the field of glycobiology, specifically to glycosyltransferases. The present invention provides structure-based design of novel glycosyltransferases and their biological applications.
The structural information of glycosyltransferases has revealed that the specificity of the sugar donor in these enzymes is determined by a few residues in the sugar-nucleotide binding pocket of the enzyme, which is conserved among the family members from different species. This conservation has made it possible to reengineer the existing glycosyltransferases with broader sugar donor specificities. Mutation of these residues generates novel glycosyltransferases that can transfer a sugar residue with a chemically reactive functional group to N-acetylglucosarnine (GlcNAc), galactose (Gal) and xylose residues of glycoproteins, glycolipids and proteoglycans (glycoconjugates). Thus, there is potential to develop mutant glycosyltransferases to produce glycoconjugates carrying sugar moieties with reactive groups that can be used in the assembly of bio-nanoparticles to develop targeted-drug delivery systems or contrast agents for medical uses.
Accordingly, methods to synthesize N-acetylglucosamine linkages have many applications in research and medicine, including in the development of pharmaceutical agents and improved vaccines that can be used to treat disease.
This application claims compositions and methods based on the structure-based design of alpha 1-3 N-Acetylgalactosaminyltransferase (alpha 3 GalNAc-T) mutants from alpha l-3galactosyltransferase (a3Gal-T) that can transfer 2'-modified galactose from the corresponding UDP-derivatives due to mutations that broaden the alpha 3Gal-T donor specificity and make the enzyme alpha3 GalNAc-T.
Application:
Development of pharmaceutical agents and improved vaccines.
Developmental Status:
Enzymes have been synthesized and preclinical studies have been performed.
Inventors: Pradman Qasba (NCI) Boopathy Ramakrishnan (NCI) Elizabeth Boeggman (NCI) Marta Pasek (NCI)
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 structure-based design of novel glycosyltransferases. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.
For Additional Information Please Contact: John Stansberry Ph.D.
NIH Office of Technology Transfer
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-5236
Email: stansbej@mail.nih.gov
Fax: (301) 402-0220
