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
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.