Design and synthesis of anti-HIV agents that inhibit the Pr55Gag membrane localization

人类免疫缺陷病毒的Pr55Gag是病毒组装所需的主要结构成分，已知与d -肌磷脂酰肌醇4,5-二磷酸（PI(4,5)P2）结合。Pr55Gag的n端MA结构域在Pr55Gag与质膜结合中起关键作用。我们设计并合成了PI(2,3,4,5,6)P5类似物，包括高度磷酸化的肌醇和各种修饰的二酰基甘油，以研究ma的结合性能。Di-C7-PI(2,3,4,5,6)P5（化合物2）对MA的结合亲和力比具有相似碳长度的PI(4,5)P2高70倍，表明PIP5类似物可能通过与PI(4,5)P2竞争MA结合来阻断Pr55Gag膜的结合。

Pr55Gag of human immunodeficiency virus, the principal structural component required for virus assembly, is known to bind D-myo-phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). The N-terminus of Pr55Gag, MA domain, plays a critical role in the binding of Pr55Gag to the plasma membrane. We designed and synthesized PI(2,3,4,5,6)P5 analogs comprising highly phosphorylated inositol and variously modified diacylglycerol to examine the MA-binding property. The binding affinity for MA of Di-C7-PI(2,3,4,5,6)P5 (compound 2) is 70-fold higher than that of PI(4,5)P2 having the similar carbon length, suggesting the possibility of the PIP5 analog to block the Pr55Gag membrane binding by competing with PI(4,5)P2 in the MA-binding.