NG-allyl- and NG-cyclopropyl-L-arginine: two novel inhibitors of macrophage nitric oxide synthase.
NG-allyl- and NG-cyclopropyl-L-arginine: two novel inhibitors of macrophage nitric oxide synthase.
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NG-烯丙基-和 NG-环丙基-L-精氨酸：两种新型巨噬细胞一氧化氮合酶抑制剂。
DOI：
10.1021/jm00084a020
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发表时间：
1992
影响因子：
7.3
通讯作者：
Marletta,MA
中科院分区：
文献类型：
--
作者：
Olken,NM;Marletta,MA
^甲基- l-精氨酸最近被证明能灭活诱导型小鼠巨噬细胞一氧化氮（NO）合成酶（Olken， NM; Rusche， K. M.; Richards，等）。k;玛丽埃塔。物化学。Biophys。共同法典，1991,177,828-833)。jV -烯丙基- l-精氨酸和jV^环丙基- l-精氨酸被合成为潜在的基于机制的酶抑制剂，以利用推定发生在活性位点的化学反应。TV^环丙基- l-精氨酸是一种有效的可逆抑制剂，其K≤7.7µ。A^-烯丙基- l-精氨酸是一种有效的可逆（K±2.1µ）和不可逆的酶抑制剂。这种不可逆抑制表现出伪一级失活动力学，为0.026 min”1,Kj= 3.4µ。l -精氨酸具有立体特异性的失活保护作用，并观察了失活率的饱和度。我们的研究表明，通过对底物l -精氨酸进行相对简单的修饰，可以实现对诱导型NO合成酶的可逆和不可逆抑制。
TV^ Methyl-L-arginine has recently been shown to inactivate the inducible murine macrophage nitric oxide ('NO) synthase (Olken, NM; Rusche, K. M.; Richards,. K.; Marietta,. A. Biochem. Biophys. Res. Commun. 1991, 177,828-833). JV-Allyl-L-arginme and jV^ cyclopropyl-L-arginine were synthesized as potential mechanism-based enzyme inhibitors to exploit the chemistry presumed to occur at the active site. TV^ Cyclopropyl-L-arginine was found to be a potent reversible inhibitor with a K¡= 7.7 µ. A^-Allyl-L-arginine was found to be both a potent reversible (K¡= 2.1 µ) and irreversible inhibitor of the enzyme. This irreversible inhibition demonstrated pseudo-first-order inactivation kinetics with= 0.026 min" 1 and Kj= 3.4 µ. Stereospecific protectionof the inactivation was afforded by L-arginine, and saturabilityof the inactivation rate was observed. Our studiesindicate that bothreversible and irreversible inhibition of the inducible" NO synthase can be achieved with relatively simple modifications of the substrate L-arginine.