Cobalamin analogues modulate the growth of leukemia cells in vitro.
Cobalamin analogues modulate the growth of leukemia cells in vitro.
复制标题
钴胺素类似物在体外调节白血病细胞的生长。
作者：
G. Mclean;P. Pathare;D. Wilbur;A. Morgan;Clive S. Woodhouse;J. Schrader;H. Ziltener
氰钴胺素类似物（CN-Cbl），与功能基团连接到各种丙酰胺基团的咕啉环或核糖核苷酸接头臂，已在钴胺素（Cbl）依赖性体外细胞生长试验中进行了评价。在该生物测定中，CN-Cbl以剂量依赖性方式支持小鼠淋巴瘤BW 5147的生长，并且Cbl载体蛋白，人脱辅基转钴胺素II，将Cbl的所需浓度降低100-1000倍。Cbl的任何化学修饰都降低了其支持细胞活力和增殖的能力，其中几种修饰完全消除了活性。所有促进生长的Cbl类似物都需要脱辅基转钴胺素II的存在，以获得细胞生长的最佳支持。通常，在咕啉环的d-位修饰的Cbl类似物和在较小程度上在B-位修饰的类似物支持细胞生长，而在e-位修饰的类似物不支持细胞生长。混合实验证明了Cbl类似物抑制细胞生长的效力的逆序。因此，Cbl类似物与修改的e-位置是有效的抑制剂，而b-类似物仅表现出部分抑制活性，在高摩尔过量，和d-类似物没有抑制活性。这些结果表明，在Cbl的e-位的修饰消除了Cbl支持细胞生长的能力，并产生了Cbl依赖性细胞生长的有效抑制剂。
Analogues of cyanocobalamin (CN-Cbl), with functional groups attached to either the various propionamide groups of the corrin ring or to the ribose-nucleotide linker arm, have been evaluated in a cobalamin (Cbl)-dependent in vitro cell growth assay. In this bioassay, CN-Cbl supported, in a dose-dependent manner, the growth of the murine lymphoma BW5147 and the Cbl carrier protein, human apo-transcobalamin II, reduced the required concentration of Cbl by 100-1000-fold. Any chemical modification of Cbl decreased its ability to support cellular viability and proliferation, with several of the modifications abrogating activity completely. All of the Cbl analogues that promoted growth required the presence of apo-transcobalamin II for the optimal support of cell growth. Generally, Cbl analogues modified at the d-position of the corrin ring and, to a lesser degree, analogues modified at the b- position supported cell growth, whereas analogues with modifications at the e-position did not support cell growth. Mixing experiments demonstrated an inverse order of potency of Cbl analogues to inhibit cell growth. Thus, Cbl analogues with modifications at the e-position were potent inhibitors, whereas b-analogues exhibited only partial inhibitory activity at high molar excess, and d-analogues had no inhibitory activity at all. These results indicate that modifications at the e-position of Cbl abolish the ability of Cbl to support cell growth and generate potent inhibitors of Cbl-dependent cell growth.
各种形式的钴胺素将人脱脂蛋白转化为全甲硫氨酸合酶的机制。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kolhouse,JF;Utley,C;Stabler,SP;Allen,RH
通讯作者：
Allen,RH
钴胺素缺乏症的临床谱和诊断。
影响因子：
20.3
作者：
Stabler,SP;Allen,RH;Savage,DG;Lindenbaum,J
通讯作者：
Lindenbaum,J
多种维生素矿物质丸中钴胺素类似物的存在和形成。
DOI：
10.1172/jci110685
发表时间：
1982
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Kondo,H;Binder,MJ;Kolhouse,JF;Smythe,WR;Podell,ER;Allen,RH
通讯作者：
Allen,RH