Peptide bond
/PEP-tide bond/
Also known as: amide bond, covalent linkage, peptidic linkage
Definition
A peptide bond is a covalent bond formed between the carboxyl group (-COOH) of one amino acid and the amino group (-NH₂) of an adjacent amino acid during protein and peptide synthesis. When this condensation reaction occurs, a water molecule (H₂O) is released, and a new C-N bond is formed. The result is a backbone chain of amino acids linked by peptide bonds, with the polypeptide chain extending from the N-terminus (the amino group at the beginning) to the C-terminus (the carboxyl group at the end). Peptides are defined as chains of amino acids joined by peptide bonds; the distinction between peptides and proteins is somewhat arbitrary, though chains of roughly 50 amino acids or fewer are typically called peptides, and longer chains are called proteins. The peptide bond gives peptides and proteins their structural integrity and is fundamental to their biological activity. The sequence of amino acids linked by peptide bonds determines the three-dimensional structure and function of the peptide.
The peptide bond has characteristics of both a single bond and a double bond (resonance) due to partial double-bond character of the C-N bond. This restricted rotation around the peptide bond influences the three-dimensional shape the polypeptide can adopt. The geometry of the peptide bond (its planar nature and restricted rotation) limits the possible conformations of the polypeptide, which in turn constrains the three-dimensional structures the peptide can form. This structural constraint is crucial because peptide function depends on its three-dimensional shape, which allows it to fit into and activate specific receptors.
Peptide bonds are susceptible to proteolytic cleavage by enzymes called proteases, which catalyze hydrolysis (breaking) of the peptide bond. This is particularly important in pharmacology because proteases in the body (including digestive enzymes, serum proteases, and cellular proteases) readily break down peptides, limiting their stability and duration of action. This is why most therapeutic peptides must be administered by injection rather than orally, and why chemical modifications that resist proteolytic cleavage are often incorporated into engineered peptides to extend their half-lives.