Macromolecular Effects in Medicinal Chemistry※

Drugs can be roughly divided into small molecule drugs (naturally extracted or chemically synthesized) and macromolecular drugs (biologics) according to molecular weight.Although small molecule drugs are still the mainstay of drug research and development (R&D) at present, the slow update rate of small molecule libraries has retained their R&D speed, thus highlighting the increasingly important position of macromolecular drugs in the future pharmaceutical market.In addition to macromolecular biologics, chemically synthesized macromolecular drugs prepared by combining small molecule drugs with natural or synthetic macromolecules have received more and more attention in recent years.Due to the unique characteristic of abundant backbone architectures and spatial framework of macromolecules, including their distinctive backbone effect and multivalent effect, as well as aggregation effect and targeting effect produced by molecular assembly, many new possibilities will be introduced into the design of medicinal chemistry.In view of this, this review will briefly introduce macromolecular effects in medicinal chemistry design, with an emphasis on new performances and functions introduced in drug design based on the backbone effects, multivalent effects, aggregation effects, and targeting effects of synthetic macromolecules.We hope this review could promote the development of chemically synthesized macromolecular drugs and provide new horizons for medicinal chemistry design.