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

作　　者：张力夫[1] 阎世英[1] 

机构地区：[1]青岛大学物理科学学院,青岛266071

出　　处：《青岛大学学报（自然科学版）》2016年第2期40-45,共6页Journal of Qingdao University(Natural Science Edition)

摘　　要：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.

关 键 词：去乙酰化酶(LpxC)抑制剂 革兰氏阴性菌 药效团模型 分子对接 抗菌药物设计 

分 类 号：R914.2[医药卫生—药物化学]