Synthetic host molecules and sequestrants as therapeutic agents

Most of the currently used synthetic drugs act as ligands of their biological macromolecules, that is, they bind to the inside of their targets such as a protein. In supramolecular chemistry terms, these are ‘guest’ molecules binding to their biological ‘host’ molecules. This approach has intrinsic limitations such as difficulties in designing antidotes of drugs or toxins without disturbing the complex biochemical network and homeostasis, designing drugs that can be used to treat inborn errors of metabolism and drugs that inhibit protein–protein interactions. Host molecules (synthetic receptors or sequestrants) by contrast offer complementary opportunities in these areas, and are currently very much under-exploited as a drug discovery approach. This review highlights the recent examples in designing host molecules as potential therapeutic agents in the areas of antidotes, antibacterial agents, drugs for metabolic disorders and anticancer agents. Further exploration of this novel therapeutic modality will help to address the gap between ‘Rule-of-5’ compliant small molecules and large biologicals.