Peptide Bond

By Peptide Information       April 21, 2025

ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE SOLELY FOR INFORMATION DISSEMINATION AND EDUCATIONAL PURPOSES.

The products provided on this website are intended exclusively for in vitro research. In vitro research (Latin: *in glass*, meaning in glassware) is conducted outside the human body. These products are not pharmaceuticals, have not been approved by the U.S. Food and Drug Administration (FDA), and must not be used to prevent, treat, or cure any medical condition, disease, or ailment. It is strictly prohibited by law to introduce these products into the human or animal body in any form.

What Is a Peptide Bond  

A peptide bond is a characteristic covalent bond in protein molecules, formed through a dehydration condensation reaction between the α-carboxyl group (α-COOH) of one amino acid and the α-amino group (-NH₂) of an adjacent amino acid. Its chemical nature is an amide bond. This linkage determines the basic backbone structure of the polypeptide chain: the amino-terminal (N-terminal) and carboxyl-terminal (C-terminal) are connected through repeating peptide bonds to form a linear sequence. Due to the formation of a p-π conjugation system between the carbonyl carbon (C=O) and imino nitrogen (-NH-) in the peptide bond, the C-N bond exhibits partial double-bond characteristics, endowing the peptide bond plane with rigid coplanar features. This provides critical structural constraints for the folding of higher-order protein structures.

Mechanism of Peptide Bond Biosynthesis  

Peptide bond synthesis occurs in ribosomes, relying on transfer RNA (tRNA) to carry amino acids. Through the pairing of anticodons on tRNA with codons on messenger RNA (mRNA), amino acids are positioned at the P site and A site of the ribosome. The amino group of the amino acid at the A site undergoes dehydration condensation with the carboxyl group of the amino acid at the P site, forming an amide bond (-CO-NH-) and releasing a water molecule. The ribosome moves along the mRNA, prompting the peptide chain to extend from the N-terminal to the C-terminal. This process is powered by GTP, with the order of amino acid linkage precisely controlled by codons to achieve directional assembly of the polypeptide chain.

Spatial Structural Features and Physicochemical Properties of Peptide Bonds  

The planar conjugated structure of the peptide bond determines its unique spatial conformation: the carbonyl oxygen and amino hydrogen are in a trans configuration, forming a bond angle of approximately 120°, which constitutes a rigid planar unit (the dihedral angle ω is close to 180°). This structural feature restricts the degrees of freedom of the dihedral angles (φ and ψ) of adjacent α-carbons, promoting the formation of regular secondary structural units in the polypeptide chain (such as α-helices, β-sheets, or β-turns). In terms of physicochemical properties, the amide group of the peptide bond can act as both a hydrogen bond donor (amino hydrogen) and acceptor (carbonyl oxygen), participating in the construction of hydrogen bond networks within proteins and between molecules. Its conjugated system exhibits characteristic absorption of ultraviolet light at wavelengths of 210–230 nm, enabling the quantification of protein concentration by ultraviolet spectrophotometry. Additionally, the chemical stability of the peptide bond makes it difficult to undergo spontaneous hydrolysis in neutral aqueous solutions, but it can be specifically cleaved under the catalysis of proteases, serving as a key target for intracellular protein degradation.

Biological Functions and Technological Applications of Peptide Bonds  

In life activities, the dynamic balance of peptide bonds maintains proteome homeostasis: on the one hand, the stability of their covalent linkages ensures the functional integrity of biological macromolecules such as enzymes and structural proteins; on the other hand, specific peptide bonds are recognized and hydrolyzed by proteases (such as the proteasome in the ubiquitin-proteasome system and lysosomal enzymes), enabling the clearance of abnormal proteins and temporal regulation of signaling molecules. In the field of biotechnology, the chemical properties of peptide bonds are widely used in polypeptide synthesis: in solid-phase synthesis, protective group strategies are employed to selectively activate the carboxyl groups of amino acids for directional peptide bond formation. Protein sequencing techniques utilize phenyl isothiocyanate to react with the N-terminal amino acid and selectively cleave the first peptide bond, enabling sequential analysis of the sequence. Furthermore, protease inhibitors developed based on peptide bond analogs block the active centers of enzymes by mimicking the conformation of natural peptide bonds, becoming an important strategy in drug design. In-depth studies on the structure-function relationship of peptide bonds continue to drive technological innovations in protein engineering, polypeptide drug development, and synthetic biology.