Combinatorial Solid-Phase Synthesis and Biological Evaluation of Cyclodepsipeptide Destruxin B as a Negative Regulator for Osteoclast Morphology
Combinatorial Solid-Phase Synthesis and Biological Evaluation of Cyclodepsipeptide Destruxin B as a Negative Regulator for Osteoclast Morphology
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DOI：
10.1021/acscombsci.6b00076
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发表时间：
2016-09-01
影响因子：
--
通讯作者：
Doi, Takayuki
中科院分区：
文献类型：
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作者：
Sato, Hiroshi;Yoshida, Masahito;Doi, Takayuki
完成了环缩酚酸肽destruxin B的组合合成及生物活性评价。环化前体通过固相肽合成经由拆分和合并方法制备，所述拆分和合并方法利用具有有色标签和嵌齿的SynPhase灯笼，随后从聚合物载体裂解。利用MNBA-DMAPO在溶液相中的大环内酯化成功地平行进行，以中等至良好的产率提供所需的64元destruxin类似物。合成的类似物的生物学评价表明，需要MeAla残基的建筑块A诱导破骨细胞样多核细胞（OCL）的所需的形态学变化，并在脯氨酸部分的R-4位的取代基的引入是耐受的形态，并可能使制备的分子探针的目标识别破骨细胞。
Combinatorial synthesis and biological evaluation of cyclodepsipeptide destruxin B have been achieved. The cyclization precursors were prepared by solid-phase peptide synthesis via a split and pool method utilizing SynPhase lanterns with colored tags and cogs, followed by cleavage from the polymer-support. Macrolactonization utilizing MNBA-DMAPO in solution-phase was successfully performed in parallel to afford the desired 64-member destruxin analogues in moderate to good yields. Biological evaluation of the synthesized analogues indicated that a MeAla residue for the building block A is required to induce the desired morphological changes in osteoclast-like multinuclear cells (OCLs), and introduction of the substituent at the R-4 position of a proline moiety is tolerated by the morphology and may enable the preparation of a molecular probe for the target identification in the osteoclasts.