Peptide Bond

A peptide bond is a type of amide covalent chemical bond linking two consecutive alpha amino acids C1 (the carbon one from the alpha amino acid’s number one) and N2 ( nitrogen number one and number two), together in the peptide or protein chain.

It can also be called a eupeptide bond to differ from an isopeptide bond , a different type of amide bond between two amino acids.


When two amino acids form a dipeptide through a peptide bond , it is a type of condensation reaction . [2] In this type of condensation, two amino acids approach each other, with the non – side chain (C1) carboxylic acid moiety of one approaching the other’s non-side chain (N2) amino part. One loses hydrogen and oxygen from its carboxyl group (COOH) and the other loses hydrogen from its amino group (NH 2 ). This reaction produces one molecule of water ( H2O) and two amino acids linked by a peptide bond (-CO-NH-). Two linked amino acids are called dipeptides.

The amide bond is synthesized when the carboxyl group of one amino acid molecule reacts with the amino group of another amino acid molecule, releasing a molecule of water (H 2 O), so the process is a dehydration synthesis reaction.

Dehydration condensation of two amino acids to form peptide bonds (red) with the removal of water (blue) .
Energy is consumed in the formation of peptide bonds, which in living organisms is obtained from ATP. Peptides and proteins are chains of amino acids held together by peptide bonds (and sometimes by some isopeptide bonds) . Organisms use enzymes to produce non – ribosomal peptides, and ribosomes to produce proteins through reactions that differ in details from dehydration synthesis.

Some peptides, such as alpha-amanitin , are called ribosomal peptides because they are made by ribosomes, [6] but many are nonribosomal peptides because they are synthesized by specialized enzymes rather than by ribosomes. For example, the tripeptide glutathione is synthesized in two steps from free amino acids by two enzymes: glutamate-cysteine ​​ligase (forms an isopeptide bond, which is not a peptide bond) and glutathione synthetase (forms a peptide bond).


A peptide bond can be broken by hydrolysis (addition of water). In the presence of water they break down and release 8–16 kJ/mol (2–4 kcal/mol) of Gibbs energy. [9] This process is extremely slow, with a half-life of between 350 and 600 years per bond at 25 °C. [10]

In living organisms, this process is generally catalyzed by enzymes known as peptidases or proteases, although there have been reports of peptide bond hydrolysis caused by conformational strain as the peptide/protein folds into the basic structure. it happens. [11] This non-enzymatic process is thus not accelerated by transition state stabilization, but by ground state instability.


The wavelength of absorption for a peptide bond is 190–230 nm [12] (which makes it particularly susceptible to UV radiation).

cis/trans isomers of the peptide group

The significant delocalization of the lone pair of electrons on the nitrogen atom gives the group a partial double bond character. The partial double bond presents the amide group planar, occurring in either the cis or trans isomers. In the unfolded state of proteins, peptide groups are free to both isomerize and adopt isomers; However, in the folded state, only one isomer is adopted at each position (with rare exceptions). The trans form is highly preferred in most peptide bonds (a ratio of about 1000:1 in the trans:cis population). However, the X-Pro peptide groups have a ratio of about 30:1, possibly because the symmetry between the two and the atoms of proline makes the cis and trans isomers nearly equal in energy (see figure below). Ca Cb

Isomerization of an X-Pro peptide bond. The cis and trans isomers are on the left and far right, respectively, separated by transition states.

The dihedral angle is indicated with the peptide group (defined by the four atoms associated with it ) ; For the cis isomer (synperiplanar structure) and for the trans isomer (antiperiplanar structure). Amide groups can isomerize about the C’–N bond between the cis and trans forms, although slowly ( 20 sec at room temperature). The transition states require that the partial double bond be broken, so that the activation energy is about 80 kilojoules/mol (20 kcal/mol). However, the activation energy can be reduced (and isomerization catalysed) that favor the single-bonded form, such as placing the peptide group in a hydrophobic environment or donating a hydrogen bond to the nitrogen atom of the X-Pro peptide group. , Both of these mechanisms are employed to reduce the activation energy.

C^{{\alpha }}-C^{{\prime }}-NC^{{\alpha }}\omega\omega = 0 ^ {{\ circ}}\omega = 180 ^ {{\circ}}\tau \sim\omega =\pm 90^{{\circ }}

Prolyl isomerase (PPIAS), a naturally occurring enzyme that catalyzes the cis-trans isomerization of X-Pro peptide bonds.

Conformal protein folding is usually much faster (typically 10–100 ms) than cis-trans isomerization (10–100 s). A non-native isomer of some peptide groups can significantly disrupt conformational folding, either slowing it down or preventing it from occurring until the native isomer is reached. However, not all peptide groups have the same effect on folding; Non-native isomers of other peptide groups may not affect folding at all.

Chemical Reaction

Due to its resonance stabilization, the peptide bond is relatively unattainable under physiological conditions, even less so than similar compounds such as esters. Nevertheless, peptide bonds can undergo chemical reactions, usually through the attack of an electronegative atom on the carbonyl carbon, breaking the carbonyl double bond and forming a tetrahedral intermediate. This is the pathway followed in proteolysis and, more commonly, in NO acyl exchange reactions such as intines. When the functional group attacking the peptide bond is a thiol, hydroxyl, or amine, the resulting molecule may be called a cycloal or more specifically, a thiacyclol, an oxacyclol, or azacyclol, respectively.