By Gary Walsh
From the major writer within the box, recognized worldwide for his paintings and his authoritative courses, the contents of this booklet were chosen in order to replicate their relative value for biopharmaceuticals. hence, round half the publication is dedicated to protein glycosylation, whereas the remaining is made of different transformations, similar to carboxylation, hydroxylation, sulfation, amidation and proteolytic processing. a last part addresses the most recent pattern of engineering the amendment trend to enhance a given biopharmceutical, providing numerous contemporary case reports of winning posttranslational engineering.This first authoritative evaluate of the subject is an crucial consultant for drug builders and drug brands with an curiosity in protein prescription drugs.
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Additional info for Post-translational Modification of Protein Biopharmaceuticals
3)Gal]n, referred to as polylactosamine chains, are a common feature of elongated O-linked glycans. , addition of Lewis and ABH glycans motifs ) to both the terminal Gal and the sub-terminal GlcNAc, yielding many diverse linear and branching structures. 3 Termination of Glycan Chains Sialylation or fucosylation terminates chain extension and these residues are commonly found as the terminal monosaccharides in both N- and O-glycans. Further modiﬁcations of the glycans, including sulfation, methylation and phosphorylation, result in further heterogeneity in the range of structures possible.
15 Kaufman, R. (1998) Post translational modiﬁcations required for coagulation factor secretion and function. Thrombosis and Haemostasis, 79, 1068–1079. 16 Bradbury, A. and Smyth, D. (1991) Peptide amidation. Trends in Biochemical Science, 16, 112–115. 17 Moore, K. (2003) The biology and enzymology of protein tyrosine-Osulfation. Journal of Biological Chemistry, 278, 24243–24246. 18 Veronese, F. and Pasut, G. (2005) PEGylation, successful approaches to drug delivery. Drug Discovery Today, 10, 1451–1458.
This is achieved enzymatically, using an a-amidating enzyme (a-AE), which is itself produced by recombinant DNA technology using a CHO cell line. Amidation forms the subject matter of Chapter 10. Sulfation is a PTM that entails the covalent attachment of a sulfate (SO3À) group, usually via selected tyrosine residues within the protein backbone . Sulfation is performed by a sulfotransferase mediated co/post-translational process, occurring in the trans Golgi network, and is predominantly associated with secretory and membrane proteins.