In vitro inhibition of membrane-mediated calcification by novel phosphonates.
In vitro inhibition of membrane-mediated calcification by novel phosphonates.
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新型膦酸盐体外抑制膜介导的钙化。
DOI：
10.1007/bf02509384
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发表时间：
1996
影响因子：
4.2
通讯作者：
Eanes,ED
中科院分区：
文献类型：
--
作者：
Skrtic,D;Eidelman,N;Golomb,G;Breuer,E;Eanes,ED
报道了一系列新型膦酸盐对离子载体引发的7：2：1磷脂酰胆碱（PC）：磷酸二鲸蜡酯（DCP）：胆固醇（Chol）脂质体模型系统中矿物发育动力学的影响。当在脂质体周围的溶液中以2.5 μmol/L或25 μmol/L的浓度存在时，所研究的膦酸盐没有显著延迟脂质体内羟基磷灰石样磷酸钙盐（HAP）的初始形成或HAP晶体穿过封闭膜的渗透。然而，一旦HAP晶体直接暴露于含膦酸盐的溶液，膦酸盐会阻碍HAP晶体随后的生长和增殖。膦酸盐抑制脂质体外沉淀的有效性强烈依赖于它们的结构。发现如果膦酸酯分子含有连接到同一个C原子的两个膦酸基团，则对释放的脂质体内晶体的活性表面生长位点的抑制作用是最有效的。在膦酸盐浓度为25 μmol/L时，确定了以下一般有效性顺序：偕双膦酸盐≥偕四膦酸盐>双酰基膦酸盐>单酰基膦酸盐>双烷基膦酸盐。在bisacylphosphonate家庭，最高的抑制作用时，观察到的五个-CH 2-基团分离的酮膦酸基团。
The effects of a series of novel phosphonates on the kinetics of mineral development in an ionophore-primed 7:2:1 phosphatidylcholine (PC): dicetylphosphate (DCP): cholesterol (Chol) liposomal model system are reported. When present at 2.5 μmol/liter or 25 μmol/liter concentrations in the solution surrounding the liposomes, the investigated phosphonates did not significantly delay the initial formation of hydroxyapatite-like calcium phosphate salts (HAP) within the liposomes or the penetration of HAP crystals through the enclosing membranes. However, the phosphonates variably retarded the subsequent growth and proliferation of the HAP crystals once they became directly exposed to the phosphonate-containing solution. The effectiveness of phosphonates in inhibiting extraliposomal precipitation strongly depended on their structure. The inhibitory action on active surface growth sites of released intraliposomal crystals was found to be the most effective if the phosphonate molecule, contained two phosphonic groups linked to the same C atom. At a phosphonate concentration of 25 μmol/liter, the, following general order of effectiveness was established: geminal bisphosphonate≥geminal tetrakisphosphonate > bisacylphosphonates > monoacyl-phosphonate > bisalkylphosphonate. Within the bisacylphosphonate family, the highest inhibitory action was observed when four of five-CH2-groups separated the ketophosphonic groups.