Thiol-disulfide interchange between cystine and N-2-mercaptoethyl-1, 3-diaminopropane as a potential treatment for cystinuria.
Thiol-disulfide interchange between cystine and N-2-mercaptoethyl-1, 3-diaminopropane as a potential treatment for cystinuria.
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胱氨酸和 N-2-巯基乙基-1, 3-二氨基丙烷之间的硫醇-二硫化物交换作为胱氨酸尿症的潜在治疗方法。
DOI：
10.1016/0003-2697(84)90304-x
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发表时间：
1984
影响因子：
2.9
通讯作者：
C. Peterson
中科院分区：
文献类型：
--
作者：
P. Blackburn;C. Peterson
放射性防护化合物WR2721是一种硫磷酸盐，口服时，在胃的酸性pH下被激活为其游离硫醇（MDP）。游离硫醇是一种黏液分解化合物，它通过黏液分子的二硫键的还原起作用。在pH 6.0和37°C的尿液中，当被分子氧氧化时，MDP和半胱氨酸的等摩尔混合物优先形成MDP和半胱氨酸之间的可溶性混合二硫化物。二硫胱氨酸与MDP发生硫-二硫交换；因此，胱氨酸晶体被有效溶解。此外，在游离硫醇的催化量存在下，MDP的二硫化物会与胱氨酸发生硫-二硫化物交换，从而溶解胱氨酸晶体。MDP与半胱氨酸混合二硫化物在pH 6.0和37℃条件下可溶于尿液，浓度至少为100mg /ml。色谱程序，允许分析MDP及其混合二硫衍生物作为MDP-磺酸描述。通过这些程序，证明单次口服WR2721的20%以MDP衍生物的形式从正常志愿者的尿液中排出。这些程序将允许评估WR2721在治疗胱氨酸尿中的作用。
The radioprotective compound WR2721 is a thiophosphate, which, when administered orally, is activated at the acid pH of the stomach to its free thiol (MDP). The free thiol is a mucolytic compound which acts via the reduction of disulfide bonds of mucin molecules. An equimolar mixture of MDP and cysteine, in urine at pH 6.0 and 37°C, when oxidized by molecular oxygen, preferentially forms the soluble mixed disulfide between MDP and cysteine. the disulfide cystine will undergo thiol-disulfide interchange with MDP; as a result, cystine crystals are effectively dissolved. Moreover, in the presence of catalytic amounts of free thiol, the disulfide of MDP will undergo thiol-disulfide interchange with cystine to dissolve cystine crystals. The mixed disulfide of MDP with cysteine is soluble in urine at pH 6.0 and 37°C to at least 100 mg/ml. Chromatographic procedures which permit the analysis of MDP and its mixed disulfide derivatives as MDP-sulfonic acid are described. By these procedures, it was demonstrated that 20% of a single oral dose of WR2721 was excreted as MDP derivatives in the urine of normal volunteers. These procedures will permit the evaluation of WR2721 in the treatment of cystinuria.