Macromolecules are those with super large molecular weights. The relative molecular mass is usually above 5,000, and can even soar to more than one million, such as proteins, nucleic acids, polysaccharides, and other biological substances that are particularly closely related to life activities, as studied in molecular biology. They are basically pieced together by simple small molecular units (called monomers). In solution, macromolecules can sometimes form substances like gels, a process often explored in a molecular laboratory. Generally speaking, compounds with a molecular weight of more than 10,000 are called macromolecular compounds or high molecular compounds. They are usually composed of many repeated structural units, most of which are linear structures, and some have a little branched structure. Substances such as proteins and nucleic acids that are extremely important for biological functions, central to molecular cell biology, are all macromolecules. For example, the basic "parts" of macromolecular proteins are amino acids. In terms of particle size, macromolecules are generally between 1 and 100 nanometers, such as proteins, nucleic acids, and some common colloids, often analyzed in molecule research.
Small molecules, as the name suggests, are natural compounds with relatively small molecular weights, usually less than 1,000 Daltons, especially those biological functional molecules with less than 400 Daltons. From a biological perspective, small molecules include some biologically active things, such as small peptides, oligopeptides, oligosaccharides, oligonucleotides, vitamins, minerals, small molecular water, and plant secondary metabolites and their degradation products, such as aglycones, flavonoids, alkaloids, etc., which are key in molecular biology products. From a nutritional perspective, if proteins, fats, sugars, vitamins, minerals, and cellulose are called "first-generation nutrients", then small molecules are "second-generation nutrients", or "second-generation nutrients" for short. The particle size of small molecules is usually less than 1 nanometer, such as common solutions, amino acids, and CO2, often studied through molecule discovery in a molecular platform.
In the field of modern medicine, small molecule drugs and macromolecule drugs are two completely different treatment methods, with significant advancements driven by molecular drug design and large molecule drug discovery. The biggest difference between them is molecular weight: small molecule drugs are usually composed of hundreds of atoms and have a molecular weight of less than 1,000 Daltons; while the molecular weight of macromolecule drugs, such as molecular antibodies, is tens of thousands or even millions. This difference directly affects their physical and chemical properties, mode of action, and clinical application, particularly in molecule development.
From the perspective of solubility, small molecule drugs are usually more "hydrophilic" and dissolve better in aqueous solutions, while large molecule drugs, developed through large molecule drug development, may be a bit troublesome to dissolve because of their large size. After entering the human body, their metabolism is also completely different: small molecule drugs are generally processed by metabolic enzymes in the liver and can be quickly excreted from the body; while large molecule drugs usually rely on more complex proteolysis or macrophage phagocytosis to clear, as researched by molecular companies.
In clinical use, small molecule drugs are more convenient to use and can be taken orally or injected into the blood circulation. Large molecule drugs usually rely on more complex methods such as subcutaneous injection or intravenous infusion, mainly because they are easily decomposed and ineffective in the gastrointestinal tract. From the perspective of mechanism of action, small molecule drugs are good at directly dealing with intracellular targets, while large molecule drugs, often developed through molecular biology and evolution studies, are more suitable for regulating receptors or immune systems on the cell surface.
In terms of safety, small molecule drugs may have some side effects due to "off-target"; while large molecule drugs are more likely to cause immune-related side effects. This also leads to different clinical application ranges: small molecule drugs are big players in the treatment of hypertension, infectious diseases and other fields, while large molecule drugs, such as those in molecular drugs, have more advantages in tumor immunotherapy, autoimmune diseases and other fields.
In the future, with the advancement of drug development technology in molecular biology of the cell, the boundary between small molecule and large molecule drugs may become increasingly blurred. Scientists are working hard to develop large molecule drugs that can be taken orally, or small molecule drugs with higher specificity, striving to combine the convenience of small molecule drugs with the targeting of large molecule drugs to benefit more patients.
Updated: Jul 24, 2025
