Blackburn P, Peterson C M
Anal Biochem. 1984 Jan;136(1):31-8. doi: 10.1016/0003-2697(84)90304-x.
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 degrees 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 degrees 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.
辐射防护化合物WR2721是一种硫代磷酸盐，口服后在胃的酸性pH条件下被激活为其游离硫醇（MDP）。游离硫醇是一种粘液溶解化合物，通过还原粘蛋白分子的二硫键起作用。在pH 6.0和37℃的尿液中，MDP和半胱氨酸的等摩尔混合物被分子氧氧化时，优先形成MDP和半胱氨酸之间的可溶性混合二硫键。二硫键胱氨酸将与MDP进行硫醇-二硫键交换；结果，胱氨酸晶体被有效溶解。此外，在催化量的游离硫醇存在下，MDP的二硫键将与胱氨酸进行硫醇-二硫键交换以溶解胱氨酸晶体。MDP与半胱氨酸的混合二硫键在pH 6.0和37℃的尿液中至少可溶解至100 mg/ml。描述了允许将MDP及其混合二硫键衍生物作为MDP-磺酸进行分析的色谱方法。通过这些方法，证明正常志愿者尿液中单次口服剂量的WR2721有20%以MDP衍生物的形式排泄。这些方法将有助于评估WR2721在胱氨酸尿症治疗中的作用。
