Peptide bond- Definition, Formation, Degradation, Examples

Peptides are short chains of amino acids that can form proteins. Amino acids are the building blocks of proteins and are linked by a chemical bond called a peptide bond. The peptide bond is formed when the carboxyl group (COOH) of one amino acid reacts with the amino group (NH2) of another amino acid, releasing a water molecule (H2O). This process is called a condensation reaction or dehydration synthesis.

The number of amino acids in a peptide can range from two to fifty. Based on the number of amino acids, peptides are classified into different types:

• Oligopeptides: Peptides with ten or fewer amino acids are called oligopeptides. For example, dipeptides have two amino acids, tripeptides have three amino acids, and tetrapeptides have four amino acids.
• Polypeptides: Peptides with more than ten amino acids are called polypeptides. Polypeptides with around 100 amino acids are then considered proteins.
• Linear peptides: Peptides that have a free NH2 end and a free COOH end are called linear peptides. For example, glycylglycine is a linear dipeptide.
• Cyclic peptides: Peptides that have a covalent bond between the NH2 end and the COOH end are called cyclic peptides. For example, cyclosporin A is a cyclic peptide with 11 amino acids.

Peptides can also be categorized according to their source (plant or animal) or their function in the human body. Some examples of peptides and their functions are:

• Vasopressin: A peptide hormone that regulates water balance and blood pressure in the body.
• Oxytocin: A peptide hormone that stimulates uterine contractions during childbirth and promotes social bonding.
• Defensins: Peptides that have antimicrobial activity and help in wound healing.
• Angiotensins: Peptides that control blood pressure and sodium retention by the kidneys.

Peptides have various applications in medicine and biochemistry. They can be used as drugs, diagnostic tools, probes, vaccines, and research materials. Peptides can be synthesized chemically or produced by biological systems such as cells or microorganisms.

A peptide bond is a special type of amide bond formed between two molecules where an α-carboxyl group of one molecule reacts with the α-amino group of another molecule releasing a water molecule. The peptide bond is also referred to as the isopeptide bond where the amide bond forms between the carboxyl group of one amino acid and the amino group of another amino acid at other positions than the alpha. The process of formation of the peptide bond is an example of a condensation reaction resulting in dehydration (removal of water).

Peptide bonds are covalent bonds that exist between any two amino acids resulting in a peptide chain. A partial double bond exists between carbon and nitrogen of the amide bond which stabilizes the peptide bond. The nitrogen involved in the bond donates its lone pair to the carbonyl group resulting in a resonance effect. The resonance is highly stabilizing as the electrons can be delocalized over multiple atoms resulting in a resonance structure. Thus, the resonance structure stabilizes the bond but also limits the rotation around the amide bond due to the partial double bond.

Peptide bonds have a planar configuration that undergoes very little movement around the C-N bond but the other single bonds on either side of the C-N bond exhibit a high degree of rotational motion.

Image Source: Wikipedia.

Formation mechanism of peptide bond

The mechanism of peptide bond formation is a dehydration synthesis process. During the formation of a peptide bond, the carboxyl group of one amino acid moves towards the amino group of another amino acid. Subsequently, one hydrogen and one oxygen atoms are lost from the carboxyl group (COOH) of the first amino acid. In contrast, one hydrogen is lost from the amino group (NH2) of the other amino acid. This results in the release of a water molecule (H2O) along with the formation of an amide bond (C-N) between the two amino acids. The process of formation of a peptide bond between two amino acids results in a dipeptide molecule.

Image Source: Wikipedia

Thus, a peptide bond is formed when the carboxyl group of one amino acid condenses with the amino group of another amino acid releasing a water molecule. The formation of the peptide bond is an endergonic reaction that requires energy, which is obtained from ATP in living beings. Because this reaction involves the removal of a water molecule, it is called a dehydration synthesis reaction.

The degradation of the peptide bond takes place through hydrolysis, thus requires the presence of water molecules. The degradation reaction is very slow as the amide bond between the amino acids is stabilized by the partial double bond.

Because of the partial double bond between carbon and nitrogen molecule, carbon atom generates a slight positive charge. In the presence of water, the OH– ions of water attack the carbon atom, which results in degradation of the peptide bond. The remaining hydrogen ion of the water then attacks the nitrogen atom resulting in the amino group.

As a result of this, the peptide molecule is cleaved into two units; one unit with the carboxyl group and another with the amino group. The degradation of the peptide is an exergonic reaction that releases about 8-16 Kjol/mole of energy.

Because the protein degradation reactions are very slow, they are usually catalyzed by proteolytic enzymes like proteases and peptidases.

• Peptide bond hydrolysis is the primary step of all protein hydrolysis reactions.
• The most common method of protein degradation is acid-catalyzed hydrolysis of the peptide bond.
• Peptide hydrolysis is also essential in some synthetic reactions where amino acids in one peptide are cleaved and transferred to another peptide, resulting in separate peptide synthesis.
• Similarly, different peptides and proteins accumulate in cells resulting in toxicity. Peptide bond hydrolysis is essential in the removal of those toxins as well.
• Peptide bond hydrolysis is also an important step in the digestion of proteins in living beings.
• Hydrolysis of peptide bond occurs in the presence of water and is catalyzed by the presence of acid.
• Peptide bond hydrolysis is one of the mechanisms of peptide bond degradation where polypeptides are either cleaved into smaller peptides, or smaller peptides are degraded into separate amino acids.
• During hydrolysis, a water molecule attacks the carbonyl carbon of the peptide bond, which has a partial positive charge due to resonance. This breaks the bond between the carbon and nitrogen atoms and forms a carboxyl group on one amino acid and an amino group on another.
• The hydrolysis reaction releases about 8–16 kJ / mol (2–4 kcal / mol) of Gibbs energy. This process is very slow, with the half life at 25 °C of between 350 and 600 years per bond.
• Because the protein degradation reactions are very slow, they are usually catalyzed by proteolytic enzymes like proteases and peptidases. These enzymes have specific sites that recognize and bind to certain amino acids or sequences and cleave the peptide bonds accordingly. For example, trypsin cleaves the peptide bond after arginine or lysine residues, while pepsin cleaves after phenylalanine, tyrosine or tryptophan residues.

Proteins are large molecules that consist of one or more chains of amino acids linked by peptide bonds. The sequence of amino acids in a protein determines its structure and function. Proteins perform various roles in living organisms, such as enzymes, hormones, antibodies, transporters, receptors, and structural components.

Some examples of proteins that contain peptide bonds are:

• Hemoglobin: This is a protein that carries oxygen in the blood. It consists of four polypeptide chains (two alpha and two beta) that each contain a heme group that binds oxygen. The polypeptide chains are held together by non-covalent interactions and peptide bonds between the amino and carboxyl groups of adjacent chains.
• Insulin: This is a hormone that regulates blood glucose levels. It consists of two polypeptide chains (A and B) that are linked by two disulfide bridges. The A chain has 21 amino acids and the B chain has 30 amino acids. The peptide bonds between the amino acids form the primary structure of insulin.
• Collagen: This is a structural protein that provides strength and elasticity to connective tissues such as skin, bone, cartilage, and tendons. It consists of three polypeptide chains (alpha 1, alpha 2, and alpha 3) that form a triple helix. Each chain has about 1000 amino acids and is rich in glycine, proline, and hydroxyproline. The peptide bonds between the amino acids form the primary structure of collagen.
• Lysozyme: This is an enzyme that breaks down bacterial cell walls. It consists of a single polypeptide chain of 129 amino acids that folds into a compact globular shape. The peptide bonds between the amino acids form the primary structure of lysozyme.

These are just some examples of proteins that contain peptide bonds. There are many more proteins with different structures and functions that are formed by peptide bonds between amino acids.

One of the best ways to understand the process of peptide bond formation is to watch a video animation that illustrates the steps involved. A video animation can help you visualize how the amino acids interact with each other and how the water molecule is released. One such video animation is available on the Khan Academy website. Here is a brief summary of what you can learn from the video:

• The video starts by showing two amino acids, glycine and alanine, in their zwitterionic forms. A zwitterion is a molecule that has both positive and negative charges on different atoms. In amino acids, the amino group (NH3+) has a positive charge and the carboxyl group (COO-) has a negative charge.
• The video then shows how the amino group of glycine attacks the carboxyl group of alanine, forming a bond between the carbon and nitrogen atoms. This is called a nucleophilic addition-elimination reaction, where a nucleophile (a molecule that donates electrons) adds to an electrophile (a molecule that accepts electrons) and then eliminates a leaving group (a molecule that departs).
• The leaving group in this case is a water molecule, which is formed by combining a hydrogen atom from the amino group and an oxygen atom from the carboxyl group. This is why the reaction is also called a condensation or dehydration reaction, as it involves the removal of water.
• The video then shows how the bond between the carbon and oxygen atoms becomes a double bond, as the electrons from the oxygen atom are pulled back to form a pi bond. This makes the oxygen atom more electronegative, meaning it attracts more electrons than the carbon atom. This creates a partial positive charge on the carbon atom and a partial negative charge on the oxygen atom.
• The video then shows how this partial charge difference affects the shape of the molecule. The carbon-nitrogen bond becomes shorter and stronger, as it has some double bond character due to resonance. Resonance is when electrons can be delocalized over multiple atoms, creating different possible structures for the same molecule. The carbon-nitrogen bond also becomes planar, meaning it lies flat on one plane. This restricts the rotation around this bond, making it rigid and stable.
• The video then shows how the other bonds around the carbon-nitrogen bond can still rotate freely, allowing for different conformations of the peptide chain. Conformations are different arrangements of atoms in space that do not involve breaking or forming bonds. The video also shows how different amino acids have different side chains (R groups) that can affect the properties and interactions of the peptide chain.

The video ends by showing how multiple amino acids can be linked together by peptide bonds to form longer chains called polypeptides or proteins. Proteins are essential biomolecules that perform various functions in living organisms, such as catalyzing reactions, transporting molecules, signaling pathways, providing structure, and regulating gene expression.

I hope this helps you understand peptide bond formation better. Is there anything else you would like me to add or change? 😊

1. What is the difference between a peptide and a protein?

- A peptide is a short-chain of amino acids that can range from two to fifty amino acids, while a protein is a long-chain of amino acids that can have more than 100 amino acids. Peptides are usually considered as the building blocks of proteins.

2. What is the role of ATP in peptide bond formation?

- ATP is the source of energy for peptide bond formation. ATP provides the energy to activate the carboxyl group of one amino acid and make it more reactive towards the amino group of another amino acid.

3. What is the effect of resonance on peptide bond stability and flexibility?

- Resonance is the phenomenon where electrons are delocalized over multiple atoms in a molecule, resulting in different possible structures. Resonance stabilizes the peptide bond by lowering its energy and making it less prone to hydrolysis. Resonance also reduces the flexibility of the peptide bond by creating a partial double bond character between carbon and nitrogen atoms, which restricts the rotation around the bond.

4. What are some examples of proteolytic enzymes that catalyze peptide bond hydrolysis?

- Some examples of proteolytic enzymes are pepsin, trypsin, chymotrypsin, elastase, carboxypeptidase, and aminopeptidase. These enzymes have specific active sites that recognize and bind to certain amino acid sequences or side chains in peptides and proteins, and cleave them at specific positions.

5. What is the biuret test and how does it detect peptide bonds?

- The biuret test is a chemical test that detects the presence of peptide bonds in a solution. The test involves adding a solution of copper sulfate and sodium hydroxide to the sample. If peptide bonds are present, the solution turns violet due to the formation of a complex between copper ions and nitrogen atoms in the peptide bonds. The intensity of the color depends on the number of peptide bonds in the sample.

Peptide bond formation video animation (Khan Academy)

One of the best ways to understand the process of peptide bond formation is to watch a video animation that illustrates the steps involved. A video animation can help you visualize how the amino acids interact with each other and how the water molecule is released. One such video animation is available on the Khan Academy website. Here is a brief summary of what you can learn from the video:

• The video starts by showing two amino acids, glycine and alanine, in their zwitterionic forms. A zwitterion is a molecule that has both positive and negative charges on different atoms. In amino acids, the amino group (NH3+) has a positive charge and the carboxyl group (COO-) has a negative charge.
• The video then shows how the amino group of glycine attacks the carboxyl group of alanine, forming a bond between the carbon and nitrogen atoms. This is called a nucleophilic addition-elimination reaction, where a nucleophile (a molecule that donates electrons) adds to an electrophile (a molecule that accepts electrons) and then eliminates a leaving group (a molecule that departs).
• The leaving group in this case is a water molecule, which is formed by combining a hydrogen atom from the amino group and an oxygen atom from the carboxyl group. This is why the reaction is also called a condensation or dehydration reaction, as it involves the removal of water.
• The video then shows how the bond between the carbon and oxygen atoms becomes a double bond, as the electrons from the oxygen atom are pulled back to form a pi bond. This makes the oxygen atom more electronegative, meaning it attracts more electrons than the carbon atom. This creates a partial positive charge on the carbon atom and a partial negative charge on the oxygen atom.
• The video then shows how this partial charge difference affects the shape of the molecule. The carbon-nitrogen bond becomes shorter and stronger, as it has some double bond character due to resonance. Resonance is when electrons can be delocalized over multiple atoms, creating different possible structures for the same molecule. The carbon-nitrogen bond also becomes planar, meaning it lies flat on one plane. This restricts the rotation around this bond, making it rigid and stable.
• The video then shows how the other bonds around the carbon-nitrogen bond can still rotate freely, allowing for different conformations of the peptide chain. Conformations are different arrangements of atoms in space that do not involve breaking or forming bonds. The video also shows how different amino acids have different side chains (R groups) that can affect the properties and interactions of the peptide chain.

The video ends by showing how multiple amino acids can be linked together by peptide bonds to form longer chains called polypeptides or proteins. Proteins are essential biomolecules that perform various functions in living organisms, such as catalyzing reactions, transporting molecules, signaling pathways, providing structure, and regulating gene expression.

I hope this helps you understand peptide bond formation better. Is there anything else you would like me to add or change? 😊

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