Aggregation kinetics of recombinant human FVIII (rFVIII).

Aggregation kinetics of recombinant human FVIII (rFVIII).
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重组人 FVIII (rFVIII) 的聚集动力学。

DOI:
10.1002/jps.20432
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发表时间:
2005
影响因子:
3.8
通讯作者:
Balasubramanian,SathyamangalamV
Balasubramanian,SathyamangalamV
中科院分区:
医学3区
文献类型:
--
作者:
Ramani,Karthik;Purohit,Vivek;Middaugh,CRussell;Balasubramanian,SathyamangalamV

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The physical phenomenon of aggregation can have profound impact on the stability of therapeutic proteins. This study focuses on the aggregation behavior of recombinant human FVIII (rFVIII), a multi‐domain protein used as the first line of therapy for hemophilia A, a bleeding disorder caused by the deficiency or dysfunction of factor VIII (FVIII). Thermal denaturation of rFVIII was investigated using circular dichroism (CD) spectroscopy and size exclusion chromatography (SEC). The dependence of unfolding on heating rate indicated that the thermal denaturation of the protein was at least partly under kinetic control. The data was interpreted in terms of a simple two‐state kinetic model, N(Native)\buildrelk\over⟶A(\rmAggregated), where k is a first‐order kinetic constant that changes with temperature, as given by the Arrhenius equation. Analysis of the data in terms of the above scheme suggested that under the experimental conditions used in this study, the rate‐controlling step in the aggregation of rFVIII may be a unimolecular reaction involving conformational changes.© 2005 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 94: 2023–2029, 2005
DOI: 10.1021/bi00222a009
发表时间: 1991-02
期刊: Biochemistry
影响因子: 2.9
作者:
M. L. Galisteo;Pedro L. Mateo;J. M. Sanchez-Ruiz
通讯作者: M. L. Galisteo;Pedro L. Mateo;J. M. Sanchez-Ruiz
DOI: 10.1021/bi012006m
发表时间: 2002-05-21
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
Krishnan, S;Chi, EY;Carpenter, JF
通讯作者: Carpenter, JF
影响因子: 11.1
作者:
B. Kendrick;John F. Carpenter;Jeffrey L. Cleland;T. Randolph
通讯作者: T. Randolph
血友病的分子病理学。
DOI: --
发表时间: 1987
期刊: The Quarterly journal of medicine
影响因子: --
作者:
A. Larner
通讯作者: A. Larner