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Monoclonal Antibody Refolding and Assembly: Protein Disulfide Isomerase Reaction Kinetics  

Park, Sun-Ho (Department of Chemical Engineering, Keimyung University)
Ryu, Dewey D.Y. (Department of Chemical Engineering, University of California)
Publication Information
Biotechnology and Bioprocess Engineering:BBE / v.8, no.2, 2003 , pp. 59-63 More about this Journal
Abstract
The protein disulfide isomerase (PDI) reaction kinetics has been studied to evaluate its effect on the monoclonal antibody (Mab) refolding and assembly which accompanies disulfide bend formation. The MAb in vitro assembly experiments showed that the assembly rate of heavy and light chains can be greatly enhanced in the presence of PDI as compared to the rate of assembly obtained by the air-oxidation. The reassembly patterns of MAb in-termediates were identical for both with and without PDI, suggesting that the PDI does not determine the MAb assembly pathway, but rather facilitates the rate of MAb assembly by promoting PDI catalyzed disulfide bond formation. The effect of growth rate on PDI activities for MAb production has also been examined by using continuous culture system. The specific MAb productivity of hybridoma cells decreased as the growth rate increased. However, PDI activities were nearly constant fur a wide range of growth rates except very high growth rate, indicating that no direct correlation between PDI activity and specific MAb productivity exists.
Keywords
monoclonal antibody; protein folding and assembly; protein disulfide isomerase; continuous culture; hybridoma;
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  • Reference
1 Formation and isomerization of disulfide bonds in proteins: Protein disulfide-isomerase /
[ Hillson,D.A.;Lambert,N.;Freedman,R.B. ] / Methods in Enzymology   DOI
2 Effect of protein and peptide inhibitors on the activity of protein disulphide isomerse /
[ Morjana,N.A.;Gilbert,H.F. ] / Biochemistry   DOI   ScienceOn
3 A kinetic analyis of hybridoma growth and metabolism in batch and continuous suspension culture: effect of nutrient concentration, dilution rate, and pH /
[ Miller,W.M.;Blanch,H.W.;Wilke,C.R. ] / Biotechnol. Bioeng.
4 The thiol-protein disulfide oxidoreductase in human mononuclear cells of blood and bone barrow /
[ Ansorge,S.;Mansfeld,H.W.;Held,C.;Broodtaerts,L.;Van Camp,B. ] / Acta Histochem.   DOI   ScienceOn
5 Role of disulfide interchange enzyme in immunoglobulin synthesis /
[ Roth,R.A.;Koshland,M.E. ] / Biochemistry   DOI   ScienceOn
6 Heavy chain binding protein recognizes incompletely disulfide-bonded forms of vesicular stomatitis virus G protein /
[ Machamer,C.E.;Doms,R.;Bole,D.G.;Helenius,A.;Rose,J.K. ] / J. Biol. Chem.
7 Catalysis of the oxidative folding of ribonuclease A by protein disulphide isomerase: Dependence of the rate on the composition of the redox buffer /
[ Lyles,M.M.;Gilbert,H.F. ] / Biochemistry   DOI   ScienceOn
8 Monoclonal antibody productivity and the metabolic pattern of perfusion cultures under varying oxygen tensions /
[ Shi,Y.;Ryu,D.D.Y.;Park,S.H. ] / Biotechnol. Bioeng.   DOI   ScienceOn
9 Protein disulphide-isomerase and the formation of native disulphide bonds /
[ Freedman,R.B.;Brockway,B.E.;Lambert,N. ] / Biochem. Soc. Trans.   DOI
10 Kinetics of recombinant immunoglobulin production by mammalian cells in continuous culture /
[ Robinson,D.K.;Memmert,K.W. ] / Biotechnol. Bioeng.   DOI
11 Redox properties and cross-linking of the dithiol/disulphide active sites of mammalian protein Disulphide Isomerase /
[ Hawkins,H.C.;Nardi,M.;Freedman,R.B. ] / Biochem. J.   DOI
12 Kinetics and specificity of homogeneous protein disulphideisomerase in protein disulphide isomerization and in thiol-protein-disulphide oxidoreduction /
[ Lambert,N.;Freedman,R.B. ] / Biochem. J.   DOI
13 Transport of secretory and membrane glycoproteins from the rough endoplasmic reticulum to the golgi /
[ Lodish,H.F. ] / J. Biol. Chem.
14 Role of protein disulphide isomerase in the expression of native proteins /
[ Freedman,R.B.;Bulleid,N.J.;Hawkins,H.C.;Paver,J.A. ] / Biochem. Soc. Symp.
15 An in vitro system for studying the kinetics of interchain disulphide bond formation in immunoglobulin G /
[ Peterson,J.G.;Dorrington,K.J. ] / J. Biol. Chem.
16 Protein disulfide isomerase: A multifunctional protein resident in the lumen of the endoplasmic reticulum /
[ Noiva,R.;Lennarz,W.J. ] / J. Biol. Chem.
17 Protein oligomerization in the ER /
[ Hurtley,S.M.;Helenius,A. ] / Ann. Res. Cell Biol.   DOI   ScienceOn
18 Structural properties of homogeneous protein disulphide-isomerase from bovine liver purified by a rapid high-yielding procedure /
[ Lambert,N.;Freedman,R.B. ] / Biochem. J.   DOI
19 Preparation and characterization of monoclonal antibody to cephalexin-synthesizing enzyme from Acetobacter turbidans /
[ Yang,C.Y.;Ryu,Y.W.;Ryu,D.D.Y. ] / Hybridoma   DOI
20 Protein disulfide isomerase: Multiple roles in the modification of nascent secretory proteins /
[ Freedman,R.B. ] / Cell   DOI   ScienceOn
21 Misfolding and aggregation of newly synthesized proteins in the endoplasmic reticulum /
[ Marquardt,T.;Helenius,A. ] / J. Cell Biol.   DOI   ScienceOn
22 Performance of mammalian cell culture bioreactor with a new impeller design /
[ Shi,Y.;Ryu,D.D.Y.;Park,S.H. ] / Biotechnol. Bioeng.   DOI
23 Endoplasmic reticulum degradation of a subunit of the asialoglycoprotein receptor in vitro /
[ Wikstrm,L.;Lodish,H.F. ] / J. Biol. Chem.
24 Catalysis of thiol/disulfide exchange: Single-turnover reduction of protein disulfide isomerase by glutathione and catalysis of peptide disulfide reduction /
[ Gilbert,H.F. ] / Biochemistry   DOI   ScienceOn
25 The reactivities and ionization properties of the active-site dithiol groups of mammalian protein disulphide isomerase /
[ Hawkins,H.C.;Freedman,R.B. ] / Biochem. J.   DOI
26 Protein folding in the cell /
[ Gething,M.;Sambrook,J. ] / Nature   DOI   ScienceOn
27 Catalysis of the oxidative folding of ribonuclease A by protein disulphide isomerase: Pre-steady-state kinetics and the utilization of the oxidizing equivalents of the isomerase /
[ Lyles,M.M.;Gilbert,H.F. ] / Biochemistry   DOI   ScienceOn
28 Comparison of the activities of protein disulphide isomerase and thioredoxin in catalysing disulphide isomerization in a protein substrate /
[ Hawkins,H.C.;Backburn,E.C.;Freedman,R.B. ] / Biochem. J.   DOI
29 Kinetic study of hybridoma cell growth in continuous culture:Ⅱ.Behavior of producers and comparison to nonproducers /
[ Frame,K.K.;Hu,W. ] / Biotechnol. Bioeng.   DOI
30 Hepatoma secretory proteins migrate from rough endoplasmic reticulum to golgi at characteristic rates /
[ Lodish,H.F.;Kong,N.;Snider,M.;Strous,G. ] / Nature   DOI   ScienceOn
31 /
[ Seinfeld,J.H.;Lapidus,L. ] / Mathematical methods in chemical engineering: Vol.3. Process modeling, estimation, and identification