骨抑素的结构改造及活性初探

STUDIES ON STRUCTURE MODIFICATION OF OSTEOSTATIN(OSN) AND THEIR BIOLOGICAL ACTIVITIES

目的 :通过结构改造寻找可耐酶解、具有较高生物利用度的骨抑素类似物 ,且使骨抑素原有的抑制破骨细胞的活性得以保存。方法 :采用集组方式进行小规模产物库合成骨抑素类似物。以维甲酸中毒大鼠为骨质疏松的动物模型 ,进行多轮次集组式筛选。综合分析实验大鼠的体重、跛行状态、全身骨折数、完整股骨数、股骨干重、股骨直径等参数 ,评价骨抑素类似物的活性。结果 :合成了 2 1个骨抑素类似物 ,其结构由氨基酸分析得到确证。筛选出 3个与骨抑素活性相近的产物 ( g ,I,r)。结论 :骨抑素分子N与C末端的结构经适当改造后 。

AIM: To search for osteostatin(OSN) analogues with enzymatic stability as the promising candidates for developing new anti osteoporosis drug.METHODS: Target compounds were synthesized on the BNR resin with pooling strategy, and their bioactivities were evaluated in vivo by determining the body weight, fractures, femoral dry weight, femoral diameter, and the numbers of integral femur in rats. RESULTS: Three (g,i and r) of twenty one analogues were found to be as active as OSN. CONCLUSION: Both residues at N and C terminal in OSN molecule could be changed properly without losing the original bioactivity. Therefore, it is possible to develop some ideal OSN surrogates with higher bioavailability as the candidate for anti osteoporosis drug.