title: Glycans of Antibodies as a Specific Site for Drug Conjugation Using Glycosyltransferases.
abstract: The therapeutic cargo molecules conjugated to a specific site on a monoclonal antibody (mAb), called antibody-drug conjugates (ADCs), are becoming powerful tools in cancer treatment. Generally, the cargo molecules conjugate at the cysteine or lysine residue of the mAb, which generally results in a highly heterogeneous ADC. Therapeutic cargo molecules need to be conjugated in a site-specific manner to the mAb so that the bioefficacy of these molecules is not compromised. The mAb (IgG1) are N-glycosylated at the conserved residue Asn(297), which is present in each heavy chain of the IgG1, near the CH2 domain of the Fc fragment. The mutant or wild-type glycosyltransferases transfer sugars with a chemical handle to the glycan molecule of IgG1, making the site-specific linking of cargo molecules possible via the chemical handle, and thus making the process an invaluable technique for the production of homogeneous ADCs.
authors.affiliation: Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, Maryland 21702-1201, United States.
authors.forename: Pradman K
authors.initials: PK
authors.lastname: Qasba
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism*; D002240:Carbohydrate Sequence; D006031:Glycosylation; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000378:metabolism*; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007074:Immunoglobulin G; D011134:Polysaccharides; D016695:Glycosyltransferases; D019158:N-Acetylneuraminic Acid