Skrtic D, Eidelman N, Golomb G, Breuer E, Eanes E D
National Institute of Dental Research's Bone Research Branch Associate Program, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, USA.
Calcif Tissue Int. 1996 May;58(5):347-54. doi: 10.1007/BF02509384.
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 micromol/liter or 25 micromol/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 micromol/liter, the following general order of effectiveness was established: geminal bisphosphonate >/= geminal tetrakisphosphonate > bisacylphosphonates > monoacylphosphonate > bisalkylphosphonate. Within the bisacylphosphonate family, the highest inhibitory action was observed when four or five -CH2- groups separated the ketophosphonic groups.
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质形成动力学的影响。当在所研究的膦酸盐以2.5微摩尔/升或25微摩尔/升的浓度存在于脂质体周围的溶液中时，并未显著延迟脂质体内类羟基磷灰石磷酸钙盐（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中，膦酸盐会不同程度地阻碍其随后的生长和增殖。膦酸盐抑制脂质体外沉淀的有效性在很大程度上取决于其结构。如果膦酸盐分子含有两个连接到同一C原子的膦酸基团，则发现其对释放的脂质体内晶体活性表面生长位点的抑制作用最为有效。在膦酸盐浓度为25微摩尔/升时，建立了以下一般有效性顺序：偕二膦酸盐≥偕四膦酸盐＞双酰基膦酸盐＞单酰基膦酸盐＞双烷基膦酸盐。在双酰基膦酸盐家族中，当酮膦酸基团被四个或五个-CH2-基团隔开时，观察到最高的抑制作用。
