A trypanosome oligopeptidase as a target for the trypanocidal agents pentamidine, diminazene and suramin

FEBS Letters

Troeberg, Linda²  Nickel, Peter⁵  Pike, Robert N.⁴  Morty, Rory E.²  Jones, Roy¹  Coetzer, Theresa H.T.²  Lonsdale-Eccles, John D.³ 

[1]Department of Development and Genetics, The Babraham Institute, Cambridge CB2 4AT, UK

[2]Department of Biochemistry, University of Natal, Private Bag X01, Scottsville 3209, South Africa

[3]Department of Biochemistry and Molecular Genetics, University of Alabama, Birmingham, AL, USA

[4]Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic. 3168, Australia

[5]Pharmazeutisches Institut, Universität Bonn, D-53121 Bonn, Germany

关键词: Protease;    Oligopeptidase;    Suramin;    Pentamidine;    Diminazene;    Trypanosoma brucei;    AMC;    7-amino-4-methylcoumarin;    Cbz;    carbobenzoxy;    DFMO;    α-dl-difluoromethylornithine;    PGK;    phosphoglycerate kinase;    Suc;    succinyl;   

DOI  :  10.1016/S0014-5793(98)00914-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

African trypanosomes contain a cytosolic serine oligopeptidase, called OP-Tb, that is reversibly inhibited by the active principles of three of the five most commonly used trypanocidal drugs: pentamidine, diminazene and suramin. OP-Tb was inhibited by pentamidine in a competitive manner, and by suramin in a partial, non-competitive manner. The inhibition of OP-Tb by a variety of suramin analogues correlated with the trypanocidal efficacy of these analogues (P = 0.03; by paired Student's t-test). Since intracellular (therapeutic) concentrations of pentamidine and suramin are reported to reach approximately 206K _i and 15K _i respectively, we suggest that these drugs may exert part of their trypanocidal activity through the inhibition of OP-Tb.

【 授权许可】

Unknown