Kadam S
Anti-infective Research Division, Abbott Laboratories, Abbott Park, Illinois, USA.
Biotechnology. 1994;26:247-66. doi: 10.1016/b978-0-7506-9003-4.50014-9.
Numerous assays have been developed over the last 40 years for the detection of novel antibacterial metabolites. I have discussed many of the successful strategies and suggested some potential targets. Although the trend toward mechanism-based assays is relatively recent, it is clear that they have had a profound impact on screening in drug discovery. Often a mechanism-based assay requires construction of specific strains and verification of the antibacterial role of the selected target. Since the conception and development of a mechanism-based screen depends upon knowledge of the specific target and perhaps a compound that affects that target, it is implicit that mode of action studies on compounds discovered through random screening may subsequently lead to new mechanistic assays. While serendipity continues to play a crucial role in any screen, target-directed assays appear to be a worthwhile approach in antibacterial screening.
在过去40年里,人们开发了许多用于检测新型抗菌代谢物的分析方法。我已经讨论了许多成功的策略,并提出了一些潜在的靶点。尽管基于机制的分析方法的发展趋势相对较新,但很明显它们对药物发现中的筛选产生了深远影响。通常,基于机制的分析需要构建特定菌株并验证所选靶点的抗菌作用。由于基于机制的筛选的构思和发展依赖于对特定靶点的了解以及可能影响该靶点的化合物,因此通过随机筛选发现的化合物的作用方式研究可能随后会导致新的机制分析,这是不言而喻的。虽然意外发现在任何筛选中仍然起着关键作用,但靶向分析在抗菌筛选中似乎是一种值得采用的方法。