Peptide formation: polycondensation reaction
Amino acid molecules have the ability to interact with each other by entering into a polycondensation reaction. As a result of this interaction, a dipeptide is formed — a primary compound consisting of two amino acid residues held together by a new covalent bond ($-CO-NH-$). Water is always released during this process.
Even if only two amino acids enter the reaction, for example, glycine (Gly) and alanine (Ala), the order in which they connect plays a crucial role. Depending on which molecule provides the amino group and which provides the carboxyl group for bond formation, two completely different structural isomers are obtained:
- Glycylalanine (Gly-Ala): the glycine residue is on the left, and the alanine residue is on the right.
- Alanylglycine (Ala-Gly): the alanine residue is on the left, and the glycine residue is on the right.
A most important property of any dipeptide is that it chemically behaves like a regular amino acid. At one end of the formed molecule, a free amino group always remains (the so-called N-terminus), and at the other, a free carboxyl group (C-terminus). The presence of these free functional groups allows the molecule to continue the condensation reaction, attaching new amino acids and increasing the chain length.
Structure of the peptide group
The uniqueness of peptides is largely determined by the properties of the amide bond itself (the CONH group). The main feature of this group is its planar structure (coplanarity).
This geometry arises due to the mesomeric effect. The unshared electron pair belonging to the nitrogen atom conjugates with the $\pi$-electrons of the adjacent carbonyl group. As a result of this electronic interaction, the bond between carbon and nitrogen partially acquires the character of a double bond. The multiplicity of the C–N bond increases, making free rotation of atoms around it impossible. This rigidity of the peptide group is a fundamental factor determining the stability and spatial conformation of all protein molecules.
Isomerism and nomenclature of peptides
Since amino acids can connect in any order, the number of possible isomers increases rapidly with chain elongation. This can be calculated using simple combinatorics rules.
If we take three different amino acids — for example, alanine, serine, and tyrosine — we can synthesize $3!$ (three factorial) from them, that is, 6 different tripeptides:
- Alanyl seryl tyrosine (Ala–Ser–Tyr)
- Tyrosyl seryl alanine (Tyr–Ser–Ala)
- Alanyl tyrosyl serine (Ala–Tyr–Ser)
- Seryl tyrosyl alanine (Ser–Tyr–Ala)
- Seryl alanyl tyrosine (Ser–Ala–Tyr)
- Tyrosyl alanyl serine (Tyr–Ala–Ser)
Nomenclature rules: When writing the structure of a peptide, it is customary to place the N-terminus (free $\alpha$-amino group) strictly on the left, and the C-terminus (free $\alpha$-carboxyl group) on the right. When forming the verbal name, all amino acid residues starting from the N-terminus receive the characteristic suffix -yl (e.g., alanyl-, seryl-). The only exception is the last (C-terminal) amino acid, which fully retains its original name (e.g., -tyrosine).
Polycondensation in practice: synthesis of capron
The principle of amide bond formation works not only in living organisms but also in the chemical industry during the production of synthetic polymers. A classic example is the production of capron fiber.
The starting monomer for its synthesis is 6-aminocaproic (or $\varepsilon$-aminocaproic) acid. During polycondensation, many such molecules connect to each other, releasing water. As a result, a long polymer chain is formed, the structure of which consists of hydrocarbon radicals sequentially linked by the exact same amide groups ($-CO-NH-$) as in natural peptides.
Briefly: answers to topical questions
What qualitative (color) reaction is used in biochemistry to detect the peptide bond?
The biuret reaction (reaction with copper salts) is used to detect the peptide bond. This method is used in qualitative analysis to prove the presence of protein. In an alkaline environment, the copper ion attaches to the peptide group, resulting in a characteristic purple coloration. Other qualitative reactions target different structures: the xanthoproteic reaction detects aromatic residues, and interaction with heavy metals detects sulfur within cysteine.
In which spatial conformation (cis- or trans-) is the peptide bond predominantly found in natural proteins?
The peptide bond in natural proteins is predominantly in the trans-configuration because this is thermodynamically favorable. This bond has a rigid planar structure in which four atoms lie in the same plane. The spatial conformation of the polypeptide chain is additionally determined by the values of the torsion angles φ (phi) and ψ (psi).
What is the exact length of the C-N bond in the peptide group compared to a normal single bond?
The exact length of the C-N bond in the peptide group is 1.32 Å. This value is intermediate between the lengths of single and double bonds. Such shortening compared to a regular single bond arises due to the mesomeric effect — the conjugation of the unshared electron pair of nitrogen with the $\pi$-electrons of the carbonyl group. As a result, the multiplicity of the C–N bond increases, making it partially double, which prevents free rotation.
Which well-known biologically active peptides (hormones) are secreted by the posterior pituitary gland?
The posterior pituitary gland (neurohypophysis) does not synthesize its own hormones, but serves as the site of their release into the blood. The following peptide neurohormones are stored there and subsequently secreted into the systemic circulation:
- Antidiuretic hormone — enhances water reabsorption in the kidneys.
- Oxytocin — accumulates along with vasopressin.
These cyclic nonapeptides are produced in the magnocellular nuclei of the anterior hypothalamus, travel down axons to the posterior pituitary, and are stored in Herring bodies.
Rule for reading a peptide: "Left to right, from N to C." The left edge (N-terminus) starts the procession, all participants receive the "-yl" suffix (losing their independence), and only the last one (C-terminus) retains its full, proud name.
Class and exam questions
Why does the peptide group have a planar structure?
Due to the mesomeric effect, the unshared electron pair of nitrogen conjugates with the pi-electrons of the carbonyl group. The C-N bond becomes partially double, which prevents rotation around it.
How to determine how many isomers can be formed from a set of amino acids?
The number of isomers is determined by the factorial formula (n!). For example, for three different amino acids, this will be 3! = 1 * 2 * 3 = 6 isomers.
How does a dipeptide fundamentally differ from the starting amino acids?
A dipeptide contains a new covalent amide (peptide) bond between the residues. At the same time, it retains the terminal amino and carboxyl groups, so it chemically continues to behave like an amino acid capable of further condensation.
What else to study on this topic
- Detailed mechanism of covalent amide bond formation
- Effect of the mesomeric effect on the chemical reactivity of the peptide group
- Spatial geometry of tripeptides and more complex structures
- Comparison of the properties of natural proteins and synthetic polyamides (using capron as an example)
Master the entire topic in the "Chemistry" course
This is a summary. The course covers everything tested in classes and exams.
- Full study guide on "Peptides" and 3,009 more pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 95 video lessons for the subject
Other topics in "Chapter 18. Major Classes of Bioorganic Compounds"
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.