Post-translational modifications (PTMs) can significantly influence the properties and functions of peptide bonds in proteins. While the peptide bond itself is less commonly a direct target of PTMs, these modifications often occur on the amino acid residues that are part of the peptide backbone, thus indirectly affecting the peptide bond. For example, phosphorylation, one of the most common PTMs, usually occurs on serine, threonine, or tyrosine residues. This addition of a phosphate group can introduce a negative charge near the peptide bond, potentially altering the local structure and dynamics of the protein. Glycosylation, another common PTM, involves attaching sugar moieties to certain amino acids, which can influence protein folding, stability, and interactions with other molecules. Additionally, PTMs such as hydroxylation or methylation can change the chemical properties of amino acid side chains, impacting the protein’s tertiary and quaternary structures. These modifications can affect protein function, interactions, localisation, and stability, demonstrating how PTMs, while not altering the peptide bond directly, can significantly influence the overall structure and function of proteins.

Peptide bond hydrolysis, the process of breaking peptide bonds with the addition of water, has significant implications in biological systems. This reaction is typically catalysed by enzymes known as proteases or peptidases. Hydrolysis of peptide bonds is crucial for various physiological processes, including protein catabolism, where proteins are broken down into their constituent amino acids. This breakdown is essential for recycling amino acids in cells, providing building blocks for new protein synthesis, and also plays a role in regulating protein function and signalling. In the digestive system, peptide bond hydrolysis is a key part of protein digestion, where dietary proteins are broken down into amino acids and small peptides, which can then be absorbed by the body. Additionally, aberrant or uncontrolled peptide bond hydrolysis can lead to diseases; for instance, excessive activity of proteases can contribute to inflammatory diseases, tissue damage, and certain neurodegenerative conditions. Understanding the regulation and mechanism of peptide bond hydrolysis is therefore vital in biochemistry and medicine, offering insights into numerous physiological processes and potential therapeutic targets.

Peptide bonds can form spontaneously outside of biological systems, but this process is typically much less efficient compared to the enzyme-catalysed reactions in living organisms. In non-biological settings, the formation of peptide bonds can be achieved through chemical synthesis methods. One common method is by using activating reagents that make the carboxyl group of an amino acid more reactive, facilitating its bonding with the amino group of another amino acid. Techniques such as solid-phase peptide synthesis (SPPS) are widely used in laboratories for the synthesis of peptides and proteins. These methods often involve protecting groups to prevent unwanted reactions and use coupling agents to drive the formation of peptide bonds. However, these chemical methods generally require specific conditions, such as the use of organic solvents, elevated temperatures, or special catalysts. In contrast, in biological systems, enzymes like peptidyl transferase efficiently catalyse peptide bond formation under mild physiological conditions. The spontaneous formation of peptide bonds in nature, outside of enzymatic control, is rare due to the high activation energy required for the reaction and the relative instability of the reactants in aqueous environments.

The partial double bond character of peptide bonds arises due to resonance, where the electrons are delocalised between the oxygen and nitrogen atoms, giving the bond characteristics of both single and double bonds. This unique feature significantly impacts protein structure in several ways. Firstly, it imposes rigidity and planarity on the peptide bond, restricting the rotation around it. This limitation is crucial for maintaining a stable protein structure. Secondly, the planarity of peptide bonds contributes to the formation of secondary structures, such as α-helices and β-pleated sheets. In these structures, the planar peptide bonds align in a specific manner, allowing for hydrogen bonding between the amide hydrogen and carbonyl oxygen of different peptide bonds, stabilising the overall structure. Additionally, the partial double bond character influences the overall conformation and folding of the protein, as certain rotations are favoured over others, leading to specific three-dimensional structures that are vital for the protein's function. Therefore, the partial double bond nature of peptide bonds is a fundamental aspect in dictating the protein's structure and function.

Enzymes play a crucial role in facilitating peptide bond formation during protein synthesis. This process, primarily occurring in the ribosome, is driven by peptidyl transferase, a ribozyme (an RNA molecule with enzymatic activity) component of the ribosome. During protein synthesis, the ribosome facilitates the alignment of the amino acid attached to the tRNA in the P site with the amino acid attached to the tRNA in the A site. Peptidyl transferase then catalyses the formation of a peptide bond between the carboxyl group of the amino acid in the P site and the amino group of the amino acid in the A site. This enzymatic action is crucial for the polymerisation of amino acids, allowing the growing polypeptide chain to be extended one amino acid at a time. Without the catalytic action of peptidyl transferase and the structural support of the ribosome, the peptide bond formation would be significantly slower and less efficient, hindering the synthesis of proteins.