Comparison of Peptide Drugs and Traditional Small-Molecule Drugs

By Cocer Peptides      29 days ago

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Peptide drugs and traditional small-molecule drugs both play significant roles in drug development and clinical applications, but they differ in terms of their mechanisms of action and application characteristics.

Figure 1 Comparison of cyclic peptide therapeutics to classical small molecules and biologics.

1. Mechanism of Action

Mechanism of action of peptide drugs: Peptide drugs typically exert their effects by binding to specific receptors in the body. Due to their structural similarity to endogenous bioactive peptides, they can specifically recognize and bind to corresponding receptors, activating or inhibiting receptor-mediated signaling pathways to regulate cellular physiological functions. Insulin is a typical peptide drug that binds to insulin receptors on the cell surface, initiating a series of signal transduction processes to promote glucose uptake and utilization by cells, thereby lowering blood glucose levels.

Some peptide drugs can mimic the functions of natural peptides. After binding to receptors on the cell surface, they regulate cellular processes such as proliferation, differentiation, and apoptosis, and are used to treat various diseases such as cancer and cardiovascular diseases. Other peptide drugs can act as substrates or inhibitors of enzymes, affecting enzyme activity and thereby regulating metabolic processes in the body.

Mechanism of action of traditional small-molecule drugs: The mechanisms of action of traditional small-molecule drugs are diverse. Many small-molecule drugs exert their effects by binding to protein targets, which can be enzymes, receptors, ion channels, etc. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin inhibit the activity of cyclooxygenase (COX), reducing prostaglandin synthesis, thereby exerting anti-inflammatory, analgesic, and antipyretic effects. The binding of small-molecule drugs to targets is typically based on intermolecular forces such as hydrogen bonds, van der Waals forces, and ionic bonds. Some small-molecule drugs can insert into the DNA double helix structure, interfering with DNA replication and transcription processes, and are used to treat diseases such as tumors. Other small-molecule drugs can regulate ion channels in cell membranes, affecting cellular electrophysiological activities. For example, antiarrhythmic drugs act on ion channels in cardiac muscle cell membranes to regulate cardiac rhythm.

2. Applications

Applications in disease treatment - Peptide drugs: Peptide drugs demonstrate unique advantages in the treatment of various diseases. In diabetes treatment, in addition to insulin, glucagon-like peptide-1 (GLP-1) analogues are another important class of peptide drugs. They promote insulin secretion, inhibit glucagon release, and delay gastric emptying, thereby lowering blood glucose levels, with advantages such as low risk of hypoglycemia and weight control. In cancer treatment, certain anticancer peptides can bind to specific receptors on the surface of tumor cells, inducing tumor cell apoptosis or inhibiting tumor angiogenesis, thereby achieving the goal of suppressing tumor growth and metastasis. In cardiovascular disease treatment, certain peptide drugs can regulate vascular tone and inhibit platelet aggregation, playing an important role in the prevention and treatment of cardiovascular diseases. Peptide drugs also have some limitations, such as low oral bioavailability, typically requiring administration via non-oral routes like injection, which to some extent limits patient convenience in medication use.

Applications in disease treatment - Traditional small-molecule drugs: Traditional small-molecule drugs are widely used in clinical settings, covering various disease areas. In the field of infection control, antibiotics and other small-molecule drugs can inhibit or kill bacteria, viruses, and other pathogens, saving countless lives. In cardiovascular disease treatment, statins inhibit HMG-CoA reductase to reduce cholesterol synthesis, thereby preventing and treating cardiovascular diseases. In the treatment of psychiatric and neurological disorders, small-molecule drugs such as antidepressants and antiepileptic drugs can regulate neurotransmitter levels or functions, thereby improving patients' symptoms. The advantages of small-molecule drugs include relatively high oral bioavailability, with most being administered orally, resulting in good patient compliance.

Sources

[1] Ji X, Nielsen A L, Heinis C. Cyclic Peptides for Drug Development[J]. Angewandte Chemie International Edition, 2023,63:e202308251.DOI:10.1002/anie.202308251.

[2] Rahman M A, Akter S, Dorotea D, et al. Renoprotective potentials of small molecule natural products targeting mitochondrial dysfunction[J]. Frontiers in Pharmacology, 2022,13:925993.DOI:10.3389/fphar.2022.925993.