Site-Specific Modification of Glycoproteins Through Transglutaminase-Mediated Conjugation
AssigneeNortheastern University
InventorsZhaohui Sunny ZHOU, Amissi SADIKI
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Abstract
Methods for making a site-specific modification of a glycoprotein are provided which preserve the charge and glycoform of the glycoprotein. One or more glycans are trimmed from the glycoprotein, while keeping a core glycan attached to the glycoprotein. The removal of the one or more glycans provides access to a targeted amino acid for a site-specific reaction. The attached core glycan can optionally be utilized for modulation of the glycoprotein, or one or more glycans or reagents can be attached to the core.
Claims56
A method for making a site-specific modification of a glycoprotein, the method comprising the steps of:
- (a) trimming a glycan linked to a glycosylation site amino acid residue of the glycoprotein, whereby a core of the glycan remains linked to the glycosylation site amino acid residue, and whereby a modification site amino acid residue of the glycoprotein becomes accessible for a reaction;
- and
- (b) conjugating a reagent to the modification site amino acid residue made accessible in step (a).
A method for modulating an effector function of an antibody, the method comprising the steps of:
- (a) trimming a glycan linked to a glycosylation site amino acid residue of the antibody using an endoglycosidase, whereby a core of the glycan remains linked to the glycosylation site amino acid residue, and whereby the effector function of the antibody is reduced or abolished;
- and
- (b) transferring a glycan substrate onto the core of the glycan using a glycosynthase or removing a fucose from the core of the glycan using a fucosidase, whereby the effector function is at least partially recovered.
Dependencies are inferred from the claim text.