The fragment-based approach is a well-established strategy for organic drug discovery. Recent studies have shown that this approach also has considerable potential in medicinal inorganic chemistry, and yet the approach has not been formally described. Here, we describe selected compounds that form (or have potential to form) intra- or inter-DNA–DNA, DNA–protein, and protein–protein crosslinks. Such dual interactions provide a powerful way to generate metal-based drugs with superior efficacies to those currently used. We demonstrate that the fragment-based approach represents an ideal way to design these bioactive compounds. In this review, we point out the limitations of current examples and delineate key components that might lead to more effective compounds (i.e., compounds that are more selective and have stronger binding affinities for specific biomolecular targets).

基于片段的方法是有机药物发现的公认策略。最近的研究表明，该方法在药用无机化学中也具有相当大的潜力，但是尚未对该方法进行正式描述。在这里，我们描述了形成（或有可能形成）DNA-内部或内部DNA-DNA，DNA-蛋白质和蛋白质-蛋白质交联的化合物。这种双重相互作用提供了一种强大的方法来产生具有比目前使用的药物更高的功效的金属基药物。我们证明基于片段的方法代表设计这些生物活性化合物的理想方法。在这篇评论中，我们指出了当前示例的局限性，并描述了可能导致更有效化合物（例如，