Studies on analogues of L-cysteine and L-cystine. I. Some structural requirements for inhibiting the incorporation of radioactive L-cystine by leukemic leukocytes.
Studies on analogues of L-cysteine and L-cystine. I. Some structural requirements for inhibiting the incorporation of radioactive L-cystine by leukemic leukocytes.
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L-半胱氨酸和L-胱氨酸类似物的研究。
DOI：
10.1182/blood.v11.1.1.1
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发表时间：
1956
期刊：
影响因子：
20.3
通讯作者：
Joseph Seifter
中科院分区：
文献类型：
--
作者：
Austin S. Weisberger;L. G. Suhrland;Joseph Seifter
氨基酸L-半胱氨酸和L-胱氨酸似乎在白细胞的代谢中具有重要作用。因此，这些氨基酸的可用性降低可能对白细胞产生重要影响。通过在与S35 L-胱氨酸孵育前将白细胞暴露于各种半胱氨酸类似物（胱氨酸），研究了减少放射性L-胱氨酸流入白血病白细胞的可能性。发现需要高度特异性的结构和空间构型来减少S35 L-胱氨酸的流入。因此，未标记的L-半胱氨酸可有效减少放射性L-胱氨酸的掺入。然而，其中存在巯基、氨基或羧基的修饰或取代的胱氨酸类似物不减少S35 L-胱氨酸的流入。此外，L-半胱氨酸的巯基和氨基的空间关系的任何改变也会导致类似物减少S35 L-半胱氨酸掺入的能力丧失。在所研究的化合物和所采用的浓度中，只有未标记的L-半胱氨酸、硒胱氨酸和苯基硒半胱氨酸是有效的。硒胱氨酸与胱氨酸相同，只是硒取代了分子中的硫。苯基硒半胱氨酸在结构上也与半胱氨酸密切相关。胱氨酸硒和苯基半胱氨酸硒减少S35 L-胱氨酸内流的作用机制尚不清楚。其他硒化合物测试是无效的。这些化合物可通过（a）与L-半胱氨酸（L-胱氨酸）的特异性细胞内受体竞争性结合，（B）使正常细胞功能所必需的酶或化合物失活，（c）改变膜渗透性或（d）硒的毒性作用来发挥其抑制作用。由于硒胱氨酸和苯基硒胱氨酸在体外低浓度下具有抑制作用，这些化合物可能对体内白血病白细胞有重要作用。
The amino acids L-cysteine and L-cystine appear to have an important role in the metabolism of leukocytes. Decreased availability of these amino acids may therefore have important effects on leukocytes. The possibility of decreasing the influx of radioactive L-cystine into leukemic leukocytes was investigated by exposing the leukocytes to various analogues of cysteine (cystine) prior to incubation with S35 L-cystine. It was found that a highly specific structural and spatial configuration is required to decrease the influx of S35 L-cystine. Thus unlabeled L-cysteine is effective in decreasing the incorporation of radioactive L-cystine. However, analogues of cystine in which there is modification or substitution of the sulfhydryl, amino or carboxyl group do not decrease the influx of S35 L-cystine. Furthermore, any alteration in the spatial relationship of the sulfhydryl and amino groups of L-cysteine also results in a loss of the ability of an analogue to decrease the incorporation of S35 L-cystine. Of the compounds studied and in the concentrations employed, only unlabeled L-cysteine, selenium cystine and phenyl selenium cysteine were effective. Selenium cystine is identical with cystine except that selenium replaces the sulfur in the molecule. Phenyl selenium cysteine is also closely related structurally to cysteine. The mechanism of action of selenium cystine and phenyl selenium cysteine in decreasing the influx of S35 L-cystine is not known. Other selenium compounds tested were ineffective. These compounds may exert their inhibitory effect by (a) competitive combination with specific intracellular receptors for L-cysteine (L-cystine), (b) inactivation of enzymes or compounds essential for normal cellular function, (c) alteration in membrane permeability or (d) a toxic effect of selenium. Since selenium cystine and phenyl selenium cystine are inhibitory in low concentrations in vitro, these compounds may have important effects on leukemic leukocytes in vivo.