Understanding Peptide Bonds

by | Jun 30, 2022 | Knowledge Center

How Is The Bond Created?

When two amino acids form a covalent bond, it creates a peptide bond.[1] The Carboxyl group of one amino acid will react with the second amino group of the other amino acid. This essentially forms a peptide bond. Due to this process, a molecule (amide) filled with water is released, and this reaction is known as a condensation reaction. This creates the peptide bond (CO-NH bond).

Now how exactly are the bonds formed? Firstly, the amino acids needed must be oriented. This is so that the carboxylic acid group from the amino acid can react with the other amino acids amine. These create a dipeptide which we know as the smallest peptide composed of two amino acids.

It is important to note that new peptides can also be formed by amino acids joining together in chains. To be considered a peptide, there must be 50 or less amino acids connected.[2] Scientists also report that “As peptide chains form between joining of the primary structure of amino acids, they may enlarge to become an oligopeptide when there are between 10 to 20 amino acids in the chain.” To be considered a polypeptide, there must be about 50 to 100 amino acids connected and if there are over 100 amino acids connected, that would be called a protein.

A peptide bond can be broken down from hydrolysis. Hydrolysis is a result of a chemical breakdown reaction to water.[3] This reaction is unhurried, and the peptide bonds, which can be formed in three ways (peptides, polypeptides, or protein), are vulnerable to breakage if they were to come in contact with metastable bonds (water). 


Looking At The Structure and Polarity Of Peptide Bonds

To discover the physical characteristics of compound bonds, researchers perform x-ray diffraction studies.[4] With this study, researchers have proven that peptide bonds are both rigid and planar.[5] The researchers describe techniques for determining the X-ray crystallographic structures of peptides: incorporation of amino acids containing heavy atoms for crystallographic phase determination, commercially available kits to crystallize peptides, modern techniques for X-ray crystallographic data collection, and free user-friendly software for data processing and producing a crystallographic structure.”
These results are due to the interaction of the amide, which is able to delocalize its sole pair of electrons into carbonyl oxygen. This primarily will affect a peptide bond structure. The N–C bond is shorter than the N–Cα bond, while the C=0 bond is longer than the carbonyl bond. There is no cis configuration in the peptide, but there is a trans configuration between the carbonyl oxygen and amide hydrogen in the peptide. A trans configuration is preferred over a cis configuration as a Cis configuration can cause a steric interaction.

In the structure of a peptide bond, free rotation can occur. Free rotations are the process of a single bond coming between a carbonyl carbon and amide nitrogen. The nitrogen, however, has a free set of electrons, and thus resonance structure can be drawn where a double bond can connect the carbon and nitrogen. The oxygen, in this case, will have a negative charge while nitrogen has a positive charge, and thus, the rotation of the peptide bond will be inhibited from the resonance structure.

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  1. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. The Shape and Structure of Proteins. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26830/
  2. Forbes J, Krishnamurthy K. Biochemistry, Peptide. [Updated 2022 Aug 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562260/
  3. Bhimrao Muley, A., Bhalchandra Pandit, A., Satishchandra Singhal, R., & Govind Dalvi, S. (2021). Production of biologically active peptides by hydrolysis of whey protein isolates using hydrodynamic cavitation. Ultrasonics sonochemistry, 71, 105385. doi:10.1016/j.ultsonch.2020.105385.
  4. Mikusinska-Planner, A., & Surma, M. (2000). X-ray diffraction study of human serum. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, 56A(9), 1835–1841. doi:10.1016/s1386-1425(00)00262-6.
  5. Spencer, R. K., & Nowick, J. S. (2015). A Newcomer’s Guide to Peptide Crystallography. Israel journal of chemistry, 55(6-7), 698–710. doi:10.1002/ijch.201400179.