Spin‐trapping agent α‐phenyl N‐tert‐butylnitrone binds to trypsin and enhances heparin‐induced inhibition of amidolytic activity and structural degradation of the enzyme

FEBS Letters

Finotti, Paola¹  Corvaja, Carlo²  Pagetta, Andrea³ 

[1] Department of Pharmacology, University of Padova, Largo E. Meneghetti 2, 35131 Padova, Italy;Department of Physical Chemistry, University of Padova, Via L. Loredan 2, 35131 Padova, Italy;Department of Organic Chemistry, University of Padova, Via F. Marzolo 1, 35131 Padova, Italy

关键词: α-Phenyl N-tert-butylnitrone;    Heparin;    Trypsin;    Bovine;    Enzyme inhibition;    Oxidation;    PBN;    α-phenyl N-tert-butylnitrone;    BAPNA;    Nα-benzoyl-DL-arginine-p-nitroanilide hydrochloride;    STI;    soybean trypsin inhibitor;   

DOI  :  10.1016/S0014-5793(99)00716-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The effects of heparin on trypsin have recently been demonstrated to involve inhibition of catalytic activity and degradation of the enzyme by means of an oxidative mechanism. The possibility that α-phenyl N-tert-butylnitrone protects heparin-induced radical formation on trypsin was investigated by measuring amidolytic activity and changes in the structure of trypsin in the presence of heparin with and without α-phenyl N-tert-butylnitrone. The results show that α-phenyl N-tert-butylnitrone does not only prevent, but it even significantly enhances effects of heparin on the enzyme. This is due to the unique property of α-phenyl N-tert-butylnitrone, independently of spin-trapping capacity, to modify the trypsin structure by binding irreversibly to the catalytic triad, at sites distinct from those to which heparin binds.

【 授权许可】

Unknown