NDLI: Towards Controlling the Glycoform: A Model Framework Linking Extracellular Metabolites to Antibody Glycosylation

Content Provider	PubMed Central
Author	Jedrzejewski, Philip M. Val, Ioscani Jimenez Del Constantinou, Antony Dell, Anne Haslam, Stuart M. Polizzi, Karen M. Kontoravdi, Cleo
Copyright Year	2014
Abstract	Glycoproteins represent the largest group of the growing number of biologically-derived medicines. The associated glycan structures and their distribution are known to have a large impact on pharmacokinetics. A modelling framework was developed to provide a link from the extracellular environment and its effect on intracellular metabolites to the distribution of glycans on the constant region of an antibody product. The main focus of this work is the mechanistic in silico reconstruction of the nucleotide sugar donor (NSD) metabolic network by means of 34 species mass balances and the saturation kinetics rates of the 60 metabolic reactions involved. NSDs are the co-substrates of the glycosylation process in the Golgi apparatus and their simulated dynamic intracellular concentration profiles were linked to an existing model describing the distribution of N-linked glycan structures of the antibody constant region. The modelling framework also describes the growth dynamics of the cell population by means of modified Monod kinetics. Simulation results match well to experimental data from a murine hybridoma cell line. The result is a modelling platform which is able to describe the product glycoform based on extracellular conditions. It represents a first step towards the in silico prediction of the glycoform of a biotherapeutic and provides a platform for the optimisation of bioprocess conditions with respect to product quality.
Related Links	http://dx.doi.org/10.3390/ijms15034492
Ending Page	4522
Page Count	31
Starting Page	4492
File Format	PDF
ISSN	14220067
e-ISSN	14220067
Journal	International Journal of Molecular Sciences
Issue Number	3
Volume Number	15
Language	English
Publisher	Molecular Diversity Preservation International (MDPI)
Publisher Date	2014-03-14
Access Restriction	Open
Rights Holder	Molecular Diversity Preservation International (MDPI)
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Spectroscopy Organic Chemistry Medicine Molecular Biology Physical and Theoretical Chemistry Catalysis Inorganic Chemistry Computer Science Applications

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