Nonpeptide

Nonpeptide is an adjective used in biochemistry and pharmacology to describe molecules that are not composed of amino acids linked by peptide bonds. The term is often used to distinguish chemical entities such as steroids, amines, lipids, and other small molecules from peptides and proteins. In physiology, many hormones and signaling molecules are either peptide-based (peptide hormones) or nonpeptide (nonpeptide hormones or small molecules).

In the context of signaling, nonpeptide can refer to endogenous hormones and neurotransmitters that are not peptides, such as steroid hormones (cortisol, aldosterone), thyroid hormones (thyroxine), and monoamine amines (epinephrine, norepinephrine). It also includes frequently studied small-molecule ligands that act on receptors, especially G protein-coupled receptors and ion channels.

In pharmacology and medicinal chemistry, nonpeptide ligands are critical because they tend to be more chemically stable, orally bioavailable, and capable of crossing biological membranes compared to peptide ligands. They can be designed to mimic or block natural signaling pathways. Examples include nonpeptide receptor antagonists and agonists such as losartan (an angiotensin II receptor blocker) or propranolol (a beta-adrenergic receptor antagonist).

The term also underscores challenges: achieving high selectivity and avoiding degradation or rapid clearance, while manufacturing and formulation considerations differ from those for peptides. The distinction between peptide and nonpeptide ligands is a convention that helps researchers categorize molecules by structure and pharmacokinetic properties rather than function alone.