Eriksson B, Oberg B, Wahren B
Biochim Biophys Acta. 1982 Feb 26;696(2):115-23. doi: 10.1016/0167-4781(82)90018-5.
Several pyrophosphate analogues have been compared for their ability to inhibit the activities of isolated cytomegalovirus (CMV) DNA polymerase, herpes simplex virus type 1 (HSV 1) DNA polymerase and calf thymus DNA polymerase alpha. The most effective inhibitors were phosphonoformate and phosphonoacetate. Although not identical, the structural requirements for compounds inhibitory to CMV and HSV-1 DNA polymerase were specific, with two negatively charged groups in close vicinity. The CMV DNA polymerase was more susceptible to certain phosphonoacetates containing bulky hydrophobic alpha-substituents than was the HSV-1 DNA polymerase. No example of the converse preference was found. The inhibition of CMV DNA polymerase by phosphonoformate, hypophosphate, alpha-hydroxyphosphonoacetate and alpha-nonylphosphonoacetate was linear non-competitive with the deoxyribonucleoside triphosphates as variable substrates. Phosphonoformate, phosphonoacetate, and to a lesser extent alpha-hydroxyphosphonoacetate, carbonyldiphosphonate and alpha-nonylphosphonoacetate also inhibited the focus formation by CMV in cell-culture.
已对几种焦磷酸盐类似物抑制分离的巨细胞病毒（CMV）DNA聚合酶、单纯疱疹病毒1型（HSV 1）DNA聚合酶和小牛胸腺DNA聚合酶α活性的能力进行了比较。最有效的抑制剂是膦甲酸和膦乙酸。虽然对CMV和HSV - 1 DNA聚合酶具有抑制作用的化合物的结构要求并不完全相同，但具有特异性，即两个带负电荷的基团彼此靠近。与HSV - 1 DNA聚合酶相比，CMV DNA聚合酶对某些含有庞大疏水α - 取代基的膦乙酸更敏感。未发现相反偏好的例子。膦甲酸、次磷酸盐、α - 羟基膦乙酸和α - 壬基膦乙酸对CMV DNA聚合酶的抑制作用与作为可变底物的脱氧核糖核苷三磷酸呈线性非竞争性。膦甲酸、膦乙酸，以及程度稍轻的α - 羟基膦乙酸、羰基二膦酸盐和α - 壬基膦乙酸也抑制了CMV在细胞培养中的病灶形成。
