Protein kinases as targets for antimalarial intervention: Kinomics, structure-based design, transmission-blockade, and targeting host cell enzymes

被引:72
作者
Doerig, C
Billker, O
Pratt, D
Endicott, J
机构
[1] Univ Glasgow, INSERM U609, Wellcome Ctr Mol Parasitol, Glasgow G12 8TA, Lanark, Scotland
[2] Univ London Imperial Coll Sci Technol & Med, Dept Sci Biol, London SW7 2AZ, England
[3] Dept Biochem, Lab Mol Biophys, Oxford OX1 3QU, England
来源
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS | 2005年 / 1754卷 / 1-2期
基金
英国医学研究理事会;
关键词
parasite; protein kinase; development; drug discovery; inhibitor; Plasmodium; malaria; Trypanosoma; toxoplasma; theileria; Entamoeba;
D O I
10.1016/j.bbapap.2005.08.027
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The surge of interest in protein kinases as targets for chemotherapeutic intervention in a number of diseases such as cancer and neurodegenerative disorders has stimulated research aimed at determining whether enzymes of this class might also be considered as targets in the context of diseases caused by parasitic protists. Here, we present an overview of recent developments in this field, concentrating (i) on the benefits gained from the availability of genomic databases for a number of parasitic protozoa, (ii) on the emerging field of structure-aided design of inhibitors targeting protein kinases of parasitic protists, (iii) on the concept known as transmission-blockade, whereby kinases implicated in the development of the parasite in their arthropod vector might be targeted to interfere with disease transmission, and (iv) on the possibility of controlling parasitic diseases through the inhibition of host cell protein kinases that are required for the establishment of infection by the parasites. (c) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:132 / 150
页数:19
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