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Applications of glycosyltransferases in the site-specific conjugation of biomolecules and the development of a targeted drug delivery system and contrast agents for MRI.

Ramakrishnan B, Boeggeman E, Qasba PK

1NCI-Frederick, Center for Cancer Research, Center for Cancer Research Nanobiology Program, Structural Glycobiology Section, Building 469, Room 221, Frederick, MD 21702, USA, 2NCI-Frederick, Center for Cancer Research, Center for Cancer Research Nanobiology Program, SAIC-Frederick, Inc., Basic Research Program, Frederick, MD 21702, USA 3NCI-Frederick, Center for Cancer Research, Center for Cancer Research Nanobiology Program, Structural Glycobiology Section, Building 469, Room 221, Frederick, MD 21702, USA +1 301 846 1934 ; +1 301 846 7149 ; qasba@helix.nih.gov.

Background: The delivery of drugs to the proposed site of action is a challenging task. Tissue and cell-specific guiding molecules are being used to carry a cargo of therapeutic molecules. The cargo molecules need to be conjugated in a site-specific manner to the therapeutic molecules such that the bioefficacy of these molecules is not compromised. Methods: Using wild-type and mutant glycosyltransferases, the sugar moiety with a unique chemical handle is incorporated at a specific site in the cargo or therapeutic molecules, making it possible to conjugate these molecules through the chemical handle present on the modified glycan. Results/conclusions: The modified glycan residues introduced at specific sites on the cargo molecule make it possible to conjugate fluorophores for ELISA-based assays, radionuclides for imaging and immunotherapy applications, lipids for the assembly of immunoliposomes, cytotoxic drugs, cytokines, or toxins for antibody-based cancer therapy and the development of a targeted drug delivery system.

Published 5 February 2008 in Expert Opin Drug Deliv, 5(2): 149-153.
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