【摘 要】
：
顶体酶是存在于精子顶体内的一种胰蛋白酶样的丝氨酸水解酶,是目前男性抗生育药物设计的潜在靶点之一.在前期对精子顶体酶同源模建的基础上,根据活性腔结构和活性位点性质,以
【机 构】
：
第二军医大学药学院药物化学教研室,
论文部分内容阅读
顶体酶是存在于精子顶体内的一种胰蛋白酶样的丝氨酸水解酶,是目前男性抗生育药物设计的潜在靶点之一.在前期对精子顶体酶同源模建的基础上,根据活性腔结构和活性位点性质,以KF950为先导化合物,设计合成了一类胍基鸟嘌呤化合物,采用核磁共振氢谱、质谱、红外光谱和元素分析等手段对其结构进行了表征,其中中间体5m的结构经X射线单晶衍射分析确证.以N-甲苯磺酰-L-赖氨酸-氯甲基酮(TLCK)为阳性对照,分别测定了目标化合物对精子顶体酶的体外抑制活性.结果表明,化合物6a～6z的酶抑制活性均强于TLCK,其中化合物6z抑制活性与KF950相当.
Acrosin is a trypsin-like serine hydrolase that exists in the acrosome of sperm and is one of the potential targets for anti-fertility drug design in males.Based on the homologous modeling of sperm acrosin, The structure of active cavity and the nature of the active sites were studied. KF950 was used as the lead compound to synthesize a class of guanidino guanine compounds. The structure of the compounds was characterized by 1H-NMR, MS, FTIR and elemental analysis. Among them, The structure of 5m body was confirmed by X-ray single crystal diffraction analysis. The inhibition of sperm acrosin in vitro by the target compounds was determined by using N-tosyl-L-lysine-chloromethyl ketone (TLCK) as a positive control The results showed that the inhibitory activity of compounds 6a ~ 6z was stronger than that of TLCK, and the inhibitory activity of compound 6z was comparable to that of KF950.
其他文献
以己二酰氯、哌嗪类化合物和二溴代物为原料,合成了一系列未见文献报道的双螺环哌嗪季铵盐类化合物.通过1HNMR,13CNMR和元素分析确定了化合物的结构.在小鼠醋酸扭体模型上初
攻击型无人机单侧发射或投放重型武器时,可将飞行控制系统看作是一个切换控制系统。针对常见的常值型和时变型两种执行器故障,提出了一种自适应观测器设计方法,同时结合状态
To evaluate the clinic outcome of off-pump coronary bypass grafting (OPCABG) of patients with coronary heart disease and chronic obstructive pulmonary disease,
从化合物5出发,首先通过C-3位羟基的转位反应制得(+)-新黄皮酰胺(1)的前体化合物4,然后经过酮羰基的还原反应合成得到(+)-新黄皮酰胺(1).提供了一种简洁的(+)-新黄皮酰胺的全
A method of screening assay is demonstrated. The approach is based on the affinity ofantitumor candidates for topoisomerases. In this method, antitumor candidat
在模拟高放废物深地质处置的低氧低浓条件下,探讨用膜过滤法研究Np胶体行为的可行性.实验研究结果表明:无腐殖酸存在时,在pH＝1～13条件下,无机离子对237Np的测定无明显影响,237N
Consumption of arsenic contaminated water and cereals is a serious threat to humans all over the world.Rice(Oryza sativa“Nipponbare”),as a main cereal crop,ca
As sessile organisms, plants encounter various environmental stimuli including abiotic stresses during their lifecycle. To survive under adverse conditions, pla
Arabidopsis thaliana L. yellow variegated (var2) mutant is defective in a chloroplast FtsH family metalloprotease, AtFtsH2/VAR2, and displays an intriguing gree
The Imitation Switch (ISWI) type adenosine triphosphate (ATP)-dependent chromatin remodeling factors are conserved proteins in eukaryotes, and some of them are