NEOPTERIN DERIVATIVES MODULATE THE NITRATION OF TYROSINE BY PEROXYNITRITE

Citation
B. Widner et al., NEOPTERIN DERIVATIVES MODULATE THE NITRATION OF TYROSINE BY PEROXYNITRITE, Biochemical and biophysical research communications (Print), 248(2), 1998, pp. 341-346
Citations number
27
Categorie Soggetti
Biology,Biophysics
ISSN journal
0006291X
Volume
248
Issue
2
Year of publication
1998
Pages
341 - 346
Database
ISI
SICI code
0006-291X(1998)248:2<341:NDMTNO>2.0.ZU;2-N
Abstract
The impact of neopterin and 7,8-dihydroneopterin on peroxynitrite-indu ced nitration of L-tyrosine was studied. Neopterin derivatives and per oxynitrite are formed during immune response. Tyrosine nitration repre sents one major effect of nitric oxide-mediated cytotoxicity. Peroxyni trite formed in situ was co-incubated with tyrosine and neopterin or 7 ,8-dihydroneopterin or other pteridine derivatives, respectively. The nitration product, 3-nitro-L-tyrosine, was measured by HPLC via UV abs orption at 360 nm. Neopterin (200 mu M) increased the nitration rate b etween pH 4.0 and 5.5 up to +60%. 7,8-Dihydroneopterin inhibited tyros ine nitration over the whole pH range examined. In a series of various pteridine derivatives, neopterin and 7,8-dihydroneopterin achieved th e strongest modulating effects on tyrosine nitration. Interactions of peroxynitrite with hydroxypropyl side chains of fully aromatic pterin derivatives may increase nitration, while partially hydrated pyrazino ring structures abate the reactivity of peroxynitrite. The results of this study suggest a potential impact of neopterin derivatives on pero xynitrite-mediated cytotoxicity. (C) 1998 Academic Press.