General info about polypeptides and other peptides

What are polypeptides

Larger polypeptides or more than one polypeptide occurring together are referred to as proteins. Proteins are polymers of amino acids that often bind to small molecules (e.g. ligands, coenzymes), to other proteins or other macromolecules (DNA, RNA, etc.). That is why the building blocks of proteins are called amino acids. Proteins have a vital role in biology and function as building blocks in muscles, bones, hair, nails and form enzymes, antibodies, muscles, connective tissue and much more. Peptides are shorter chains of amino acids (two or more), which distinguishes them from polypeptides, which are much longer.


Polypeptic structure

A polymer produced by a living organism is called a biopolymer. There are four major classes of biopolymers: (1) polysaccharides, (2) polypeptides, (3) polynucleotides, and (4) fatty acids. What polymers consist of amino acids? A polypeptide is an unbranched chain of amino acids linked by peptide bonds. The peptide bond joins the carboxyl group of one amino acid to the amine group of the next amino acid to form an amide. What are peptides? Short polypeptides can be named based on the number of monomeric amino acids that comprise them. For example, a dipeptide is a peptide consisting of two amino acid subunits, a tripeptide is a peptide consisting of three amino acid subunits, and a tetrapeptide is a peptide consisting of four amino acid subunits.


Amino Acid definition

The amino acids that make up polypeptides contain an alkali amino group (-NH2), an acidic carboxyl group (-COOH) and an R group (side chain). The R group is variable in its components and is unique to each amino acid. Each amino acid molecule contains a carbon atom (α-carbon). In most cases, the amino and carboxyl groups are attached to the α-carbon (Figure 2).


Peptides connection definition

A peptide bond (amino acid bond) is the bond between amino acids. This forms the primary structure of a long polypeptide chain. Proteins consist of one or more polypeptides that have interacted together to form the final, stable, functioning conformation.


Structure of an amino acid

Figure 2. The structure of an amino acid. Credit: Scott Henry Maxwell – (diagram), CC BY-SA 4.0

Amino acids can either be α-amino acids or β-amino acids. Where both the carboxyl and amino groups are attached to the central carbon, they are known as α-amino acids. In β-amino acids, the carboxyl and amino groups are attached to another carbon molecule.


There are 21 amino acids used by eukaryotes to form proteins (protein synthesis). All vary by differences in their side chains. Humans and other vertebrates can make 12 of these, which are called non-essential amino acids. The remaining 9 amino acids must be consumed, as they cannot be made in the body, but are made by other organisms. These are called essential amino acids.


Until recently, the list of amino acids was composed of 20. However, selenocysteine ​​was added as the 21st amino acid in 1986. Selenocysteine ​​is found in some rare proteins in bacteria and humans. Even more recently, it was proposed that pyrrolysine should be called the 22nd amino acid. However, pyrrolysine is not used in human protein synthesis. Table 1 shows the lists of essential and non-essential amino acids. Figure 4 illustrates the structure of 21 amino acids.


Table 1: Essential og Nonessential Amino Acids

Essential Amino Acids

Nonessential Amino Acids




Aspartic Acid


Glutamic Acid






















Polypeptidernes formation

The variation of the side chains of the R group changes the chemistry of the amino acid molecule. Most amino acids have side chains that are nonpolar (do not have positive and negative poles). Others have positively or negatively charged side chains. Some have polar side chains that are uncharged. The chemistry of the side chain affects how the amino acids are linked together to form the final protein structure.


If the amino acids have charged side chains, they can form ionic bonds. If the side chains are hydrophobic, they can be linked by van der Waals interactions. Polar amino acids can be joined by hydrogen bonds. Therefore, side chain interactions of a long chain of amino acids and their order in the chain will determine how the protein molecule is formed, i.e. where it folds. More information about the various bonds and interactions between the amino acids will be discussed later in this section.


Proteins have 4 levels of structure: the primary structure, the secondary structure, the tertiary structure, and the quaternary structure.


The primary structure

What is a polypeptide sequence? Simply put, polypeptides are chains of amino acids. The primary structure of a protein begins with the formation of peptide bonds between amino acids, resulting in the formation of a peptide.


What is a peptide bond? Peptide bonds exist between the α-carboxyl group of amino acids and the α-amino group of different amino acids. This forms a stable two-dimensional structure with side chains extending from the polypeptide chain. This allows the side chains to interact with other molecules. This act of linking smaller units together to create a longer polymer is known as polymerization. How are peptide bonds formed? The reaction between two amino acids joining together is a condensation reaction. This is because a hydrogen and oxygen molecule is lost from the carboxyl group of 1 amino acid, and a hydrogen molecule is lost from the amino group of another amino acid. This produces a water molecule (H2O), hence the term condensation reaction.


No. 2 primary structure

The secondary structure is formed when hydrogen bonds form between atoms in the polypeptide backbone (this does not include the side chains). Two common patterns that arise from repeated folding via hydrogen bonding are the α-helix and the β-folded sheet.


In the α-helix secondary structure, the coil is right-handed and the hydrogen bonds are between every fourth amino acid. α-keratin is an example of a protein composed of α-helices. This protein is found in hair and nails.


The β-folded sheet is the other common secondary structure. This happens when two polypeptide chains lie next to each other and hydrogen bonds form between them. There are two types of β-pleated sheets; these are the parallel β-pleated sheet and the antiparallel β-pleated sheet. At the end of a polypeptide there is either a free carboxyl group or a free amino group.


In a parallel β-folded sheet, the two polypeptide chains run in the same direction with the same group at each end. In an anti-parallel β-folded sheet, the polypeptides run in different directions.


A less commonly known secondary structure is the β-barrel. In this case, the polypeptides run anti-parallel to each other but have also twisted into a barrel shape with hydrogen bonds between the first and last amino acids


No. 3 primary structure

The tertiary structure of the polypeptide is defined as the 3-dimensional structure. The protein begins further folding as a result of side chain (R-group) interactions in the primary sequence. This is via hydrophobic bonds, hydrogen bonds, ionic bonds, disulfide bonds and Van der Waals interactions.


Polypeptide vs protein: at this point the polypeptide structure is called a protein because it has formed a functional conformation.

-Hydrophobic bonds - side chains that are non-polar and the hydrophobic groups together. They remain on the inside of the protein, leaving hydrophilic side chains on the outside that are in contact with water.

-Hydrogen bonds - occur between an electronegative atom and a hydrogen atom that is already bonded to an electronegative atom. They are weaker than covalent bonds and ionic bonds, but stronger than van der Waals interactions.

-Ionic bonds - a positively charged ion forms a bond with a negatively charged ion. [a]These bonds are stronger on the inside of a protein where water is excluded, as water can dissociate these bonds.

-Van der Waals interactions - this refers to electrical interactions between close atoms or molecules. These interactions are weak, but having more of these interactions in a protein can increase its strength.

-Disulfide bond - this is a type of covalent bond and is also the strongest bond found in proteins. It involves the oxidation of 2 cysteine ​​residues, resulting in a sulfur-sulfur covalent bond. Almost one-third of eukaryotic synthesized proteins contain disulfide bonds. These bonds provide stability to the protein. Figure 8 shows the various bonds involved in the tertiary structure of a protein.


No. 4 primary structure

In the quaternary structure, chains of polypeptides begin to interact together. These protein subunits bind together via hydrogen bonds and van der Waals interactions. Their arrangement allows the specific functionality of the final protein. Changes in conformation can be detrimental to their biological actions. Hemoglobin is an example of a protein with a quaternary structure. It is made up of 4 subunits.


It is worth noting that not all proteins have a quaternary structure, many proteins only have a tertiary structure as their final conformation.


Are polypeptides proteins? In some cases, the word polypeptide is used interchangeably with the word protein. However, a protein can consist of more than 1 chain of polypeptides, so it is not always correct to use the term polypeptide for all proteins.


The function of polypeptides as an example

Polypeptides and their resulting proteins are found throughout the body. What is the function of a polypeptide? The roles of the polypeptides depend on the amino acid content. There are over 20 amino acids, and the average length of a polypeptide is about 300 amino acids. These amino acids can be arranged in any given sequence. This allows for a massive number of possible protein variations. However, not all of these proteins would have a stable 3D conformation. The proteins found in cells are not only stable in their conformation, but also unique to each other.


What are examples of polypeptides? The most important examples of proteins include transporters, enzymes, hormones and structural support.



There are protein transporters and peptide transporters. Peptide transporters are found in the peptide transporter (PTR) family. Their function is to act as membrane proteins in a cell to take up small peptides (di- or tri-peptides). There are 2 main types of peptide transporters, PEPT1 and PEPT2. PEPT1 is found in intestinal cells and helps with the absorption of di- and tripeptides. PEPT2 on the other hand is mainly found in the kidney cells and helps in the reabsorption of di- and tripeptides.



Polypeptides also constitute enzymes. Enzymes initiate (catalyze) or accelerate biochemical reactions. They are biomolecules that help in the synthesis as well as the breakdown of molecules. All living organisms use enzymes and they are essential for our survival. It is believed that enzymes catalyze about 4000 different biochemical reactions in life. All enzymes are named with the suffix -ase. There are 6 functional groups of enzymes: oxidoreductases, transferases, hydrolases, lyases, isomerases and ligases. Lactase, for example, is a hydrolase that causes the hydrolysis (breakdown reaction with water) of lactose (milk sugar) into galactose and glucose monomers. Lactase is found in humans and animals and has the function of helping with the digestion of milk. It is also found in some microorganisms.



Hormones can be either steroid-based or peptide-based. Polypeptide and protein hormones vary in their size, with some consisting of only a few amino acids, while others are large proteins. They are made in cells of the rough endoplasmic reticulum (RER) and then moved to the Golgi apparatus. They are then placed in vesicles until needed/stimulated for secretion outside the cell.


Insulin is an example of a protein hormone. It is 51 amino acid residues in length and is composed of 2 polypeptide chains known as chain A and chain B. The beta cells of the pancreas synthesize this hormone. Insulin helps the body regulate blood sugar levels by removing excess glucose from the blood and allowing it to be stored for later use.


Protection of the structure

Finally, structural proteins provide shape and support to living organisms. For example, they can provide support in a cell wall. They are also found in connective tissue, muscles, bones and cartilage. Actin is an example of a structural protein found in cells. It is the most abundant protein found in eukaryotic cells. In muscle cells, they help support muscle contraction. They also form the cytoskeleton of cells that help them keep their shape. In addition, actin is involved in cell division, cell signaling and organelle movement.



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