Ilic Stefan, Cohen Shira, Singh Meenakshi, Tam Benjamin, Dayan Adi, Akabayov Barak
Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Antibiotics (Basel). 2018 Aug 13;7(3):72. doi: 10.3390/antibiotics7030072.
The bacterial primase-an essential component in the replisome-is a promising but underexploited target for novel antibiotic drugs. Bacterial primases have a markedly different structure than the human primase. Inhibition of primase activity is expected to selectively halt bacterial DNA replication. Evidence is growing that halting DNA replication has a bacteriocidal effect. Therefore, inhibitors of DNA primase could provide antibiotic agents. Compounds that inhibit bacterial DnaG primase have been developed using different approaches. In this paper, we provide an overview of the current literature on DNA primases as novel drug targets and the methods used to find their inhibitors. Although few inhibitors have been identified, there are still challenges to develop inhibitors that can efficiently halt DNA replication and may be applied in a clinical setting.
细菌引发酶——复制体中的一个重要组成部分——是新型抗生素药物一个有前景但未得到充分利用的靶点。细菌引发酶的结构与人类引发酶明显不同。预计抑制引发酶活性可选择性地阻止细菌DNA复制。越来越多的证据表明，阻止DNA复制具有杀菌作用。因此，DNA引发酶抑制剂可提供抗生素药物。已经采用不同方法开发出了抑制细菌DnaG引发酶的化合物。在本文中，我们概述了关于作为新型药物靶点的DNA引发酶的当前文献以及用于寻找其抑制剂的方法。尽管已鉴定出的抑制剂很少，但开发能够有效阻止DNA复制并可应用于临床的抑制剂仍存在挑战。
