抗革兰氏阴性菌去乙酰化酶LpxC抑制剂设计

Inhibitor Design of LpxC Inhibitors Anti Gram Negative

以18种文献报道的脱乙酰基酶(UDP-3-O-(R-3-hyrdoxymyristoyl)-N-acetyl glucosamine,LpxC)抑制剂作为训练集,用Discovery Studio3.0构建了LpxC抑制剂的三维药效团模型,所得的最优药效团Hyphothesis1具有较好的预测性和置信度。用该药效团模型对SPECS数据库进行搜索,从中选取打分值较高的化合物对接到LpxC活性位点,根据PLP1打分函数筛选出15个打分较高的化合物,为设计抗革兰氏阴性菌的新型LpxC抑制剂提供了理论参考。

3D QSAR Pharmacophores of UDP-3-O-（R-3-hyrdoxymyristoyl）-N-acetyl glucosamine（LpxC）inhibitors were built using Discovery Studio 3.0with a training set consisted of 18 LpxC inhibitors reported,in which hypothesis1 showed considerable qualities of both predictability and confidence as a most pharmacophore.High scored compounds were gained through a screening by SPECS database,hypothesis1 filtered,then further docked into active site of a LpxC crystal structure where 15 compounds of the highest score were obtained based on PLP1 scoring function,led to improved novel drug design for LpxC inhibitors against Gram negatives.