Characterization of the glycosylation occupancy and the active site in the follow-on protein therapeutic: TNK-tissue plasminogen activator.

ABSTRACT: TNK-tPA products from the innovator and follow-on manufacturers were characterized and compared. All tryptic peptides including N-terminal, C-terminal, and mutated peptides as well as the disulfide-linked peptides were identified, with the demonstration of the same primary sequence and disulfide linkages between the innovator and follow-on products. The three N-linked and one O-linked fucose glycosylation sites were identified. The two N-linked fucose sites (N103 and N448) and one O-linked fucose site (T61) were fully glycosylated in both innovator and follow-on products. The other N-linked site (N184) was partially glycosylated and exhibited a approximately 2.5-fold difference between the innovator (60% occupancy) and follow-on (25% occupancy) products. Since the glycosylation occupancy a

SUBMITTER: Jiang H 

PROVIDER: S-EPMC3104925 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature