KINETIC ASPECTS OF STRUCTURE-ACTIVITY RELATIONS - BINDING OF SULFONAMIDES BY CARBONIC-ANHYDRASE
KINETIC ASPECTS OF STRUCTURE-ACTIVITY RELATIONS - BINDING OF SULFONAMIDES BY CARBONIC-ANHYDRASE
复制标题
DOI：
10.1098/rspb.1976.0034
复制
发表时间：
1976-01-01
期刊：
影响因子：
--
通讯作者：
BURGEN, ASV
中科院分区：
文献类型：
--
作者：
KING, RW;BURGEN, ASV
研究了磺胺类药物与[人红细胞]碳酸酐酶结合的快速动力学。对六个磺胺类同系物进行了研究。在所有情况下，同源系列中结合常数的增加主要是由于缔合速率常数的增加。间位和邻位取代磺胺类化合物的结合常数较低，主要是由于缔合速率常数较低所致。用特异性亲和法测定了磺胺类药物与脱碳酸酐酶的结合。同源序列对脱辅酶的影响在很大程度上是重现的，但位置异构化的影响不是；结合过程是pH不敏感的。有证据表明，磺胺类药物与碳酸酐酶的结合过程涉及一个中间的非配位络合物，然后将其转化为最终的配位络合物。根据对中间络合物稳定性、异构化成配位络合物的速率和解离速率常数的影响，考察了磺胺类化合物与碳酸酐酶结合的构效关系。
The fast kinetics of binding of sulfonamides to [human erythrocyte] carbonic anhydrase were examined. Six homologous series of sulfonamides were studied. In all cases the increase in binding constant in a homologous series is due mainly to an increase in the association rate constant. Meta- and ortho-substituted sulfonamides have lower binding constants, mainly due to a lower association rate constant. The binding of sulfonamides to apocarbonic anhydrase was measured by a specific affinity method. The effects of homologous series are largely reproduced on the apoenzyme, but the effects of positional isomerization are not; the binding process is pH-insensitive. Evidence is presented that the binding process for sulfonamides and carbonic anhydrase involves an intermediate non-coordinate complex which is then converted into the final coordinate complex. Structure-activity relations in the binding of sulfonamides to carbonic anhydrase are examined on the basis of effects on the stability of the intermediate complex, the rate of isomerization into the coordinate complex, and the dissociation rate constant.