Imperial College London
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Professor Cleo Kontoravdi

Faculty of Engineering, Department of Chemical Engineering

Professor of Biological Systems Engineering
 
 
 
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Contact

 

+44 (0)20 7594 6655cleo.kontoravdi98 Website

 
 
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Location

 

310ACE ExtensionSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Jedrzejewski:2014:10.3390/ijms15034492,
author = {Jedrzejewski, PM and Jimenez, del Val I and Constantinou, A and Dell, A and Haslam, SM and Polizzi, KM and Kontoravdi, C},
doi = {10.3390/ijms15034492},
journal = {International Journal of Molecular Sciences},
pages = {4492--4522},
title = {Towards controlling the glycoform: a model framework linking extracellular metabolites to antibody glycosylation},
url = {http://dx.doi.org/10.3390/ijms15034492},
volume = {15},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Jedrzejewski,PM
AU  - Jimenez,del Val I
AU  - Constantinou,A
AU  - Dell,A
AU  - Haslam,SM
AU  - Polizzi,KM
AU  - Kontoravdi,C
DO  - 10.3390/ijms15034492
EP  - 4522
PY  - 2014///
SN  - 1422-0067
SP  - 4492
TI  - Towards controlling the glycoform: a model framework linking extracellular metabolites to antibody glycosylation
T2  - International Journal of Molecular Sciences
UR  - http://dx.doi.org/10.3390/ijms15034492
UR  - http://hdl.handle.net/10044/1/63403
VL  - 15
ER  -
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