Applications of “linkers” in fragment-based drug design

Fragment-based drug discovery, as a complementary method to traditional screening, has a broad momentum of development in academia, as well as large pharmaceutical companies and biotechnology laboratories. It is used to select favorable combinations of fragments or extend new drug molecules to obtain highly active drug candidates. The strategies used to develop active molecules from fragments are usually three approaches: growth, ligation and incorporation, where the ligation approach provides a theoretical opportunity for rapid access to binding energy. Here, we highlight linkers with different types and classifications that have been published in the past ten years, and explain how these linkers are designed and introduced into lead compounds to obtain potential candidate compounds.