Over the last few decades it has been shown that specific peptide sequences found in foods can exert health beneficial properties. Some have even been proven effective in treating disease.
The classical approach to producing these bioactive peptides involves finding a protein source, hydrolyzing it either by enzymes or fermentation, and identifying the desired peptide sequence with a potential bioactivity. This is a labor intensive process.
The amino acids that form the building blocks of proteins are bonded together to create peptides. There are 20 different amino acids, and each has a carbon, hydrogen, oxygen and nitrogen atom attached to it with a side group that gives the amino acid its shape and unique properties. Amino acids link together to form chains that are then folded to create a protein structure. Human adult cells can produce 11 of the 20 amino acids, but the remaining nine must be consumed in the diet or through supplements. Amino acids also act as the building blocks of other substances, such as hormones and neurotransmitters.
The simplest of these are the amino acid monomers, which have a carboxyl group (-COOH), an amino group and a single hydrogen atom. The different side groups give them different properties and allow them to bond with other molecules, such as other amino acids or lipids. When two or more amino acid monomers link together they form a peptide chain, which is then folded to create a protein structure.
Recent scientific research has shown that specific peptide sequences found in food proteins have health beneficial functions. Unlike synthetic drug molecules that are usually pure, most bioactive peptides found in foods and their hydrolysates consist of a mixture of peptides with varying degrees of activity. As such, it is not feasible to extract and purify these peptides to a high degree of purity in order to obtain a commercial product with defined biological activity.
In most advanced economies, regulatory systems exist to protect the public’s health and safety. These include governmental approvals to market new products that have the potential to perform functions beyond their nutritional and sensory characteristics, such as bioactive peptides and food protein hydrolysates.
Bioactive peptides derived from foods or food protein hydrolysates would fall under the category of natural health products (NHP) or novel foods, which are subject to less stringent regulatory requirements than pharmaceuticals. In contrast, short peptides that are synthesized in the laboratory and purified to high levels would be classified as drugs and would require extensive and costly clinical trials before they could be marketed.
Peptide bonds are one of the strongest organic chemical bonds in nature, and they are responsible for linking amino acids into chains called polypeptides or proteins. The peptide bond is created by a condensation reaction in which the amine group of one amino acid reacts with the carboxyl group of another amino acid. The result is the formation of a four-atom functional group, which is an amide (CO-NH). The peptide bond is able to exist because the atoms involved in its formation have partial positive charge groups—the polar hydrogen atoms of amino acids—and partial negative charge groups—the polar oxygen atoms of carboxyl acids. The two amino acids are covalently bonded to each other through the peptide bond, and the amino acids are linked together by a series of links known as a backbone.
The peptide bond is very stable because of the resonance structure that forms between its two atoms. The resulting amide has the characteristics of a partially double bond between carbon and nitrogen, and the C-N bond is stabilized by sharing electrons with those from the N-H bond. This results in a strong, kinetically fast bond that is very resistant to chemical cleavage. It is only broken by exposure to strong acids or bases for a long time at elevated temperature, or by certain specific enzymes, such as digestive enzymes.
Peptides have unique properties because they contain a mixture of both simple and complex molecules. Because a peptide contains an amide bond, it is capable of carrying a small amount of negative charges and can therefore attract hydrogen from other molecules, including water molecule. This is a useful property when the peptide needs to be dissolved from a solid, such as a protein.
The peptide bond is also rigid and planar, which helps to stabilise protein structures. The peptide bond can only rotate in a limited way around the axis that connects the amino acids, allowing the peptide backbone to assume only a few positions—the cis and trans configurations. This restriction on rotation also helps to reduce steric hindrances between adjacent amino acid side chains, which is important in protein structure.
The amino acid sequence determines the structure of a protein. But the specific three-dimensional shape of a protein requires additional structural information, provided by interactions between amino acid side chains. In addition, the protein’s shape may be altered by the environment in which it is located. For these reasons, protein structures are described as primary, secondary, tertiary and quaternary.
The polypeptide chain is flexible, but its conformation (its shape) is largely determined by the interactions of amino acids with one another and with other molecules. This conformational flexibility is made possible by the peptide bond. The peptide bond is a covalent bond between the carbonyl oxygen atom of one amino acid and the carboxyl group of another amino acid. The peptide bond is planar, which gives the polypeptide chain some rigidity.
However, steric interference also limits the flexibility of a polypeptide chain. For example, the short distance between the peptide bond and the carbonyl nitrogen or carbonyl oxygen of an adjacent amino acid prevents rotation of this region of the molecule. The bonds between amino acids are also in a limited number of stable positions, which makes the overall structure rigid.
The structure of a polypeptide chain can be further stabilized by hydrogen bonding. The donor and acceptor groups of a peptide bond are the oxygen atoms in the carboxyl group of one amino acid and the hydrogen atoms in the amino group of another amino acid four amino acids farther along the chain. This is the fundamental mechanism by which helices and beta sheets form in proteins.
A protein’s secondary structure is the regular pattern of alpha or beta folding that occurs as it folds into its three-dimensional, functional state. This is a direct consequence of the collapse of the hydrophobic R-groups from contact with water and results in a dynamic, molten globule state. The formation of regular secondary structures is cooperative and is limited to a small region within the polypeptide chain because the H bonds require high energy.
In order to find peptides with particular activities, it is useful to understand the protein-level processes that drive their formation and the structure-activity relationships that determine their utilization by the body. This is the basis of quantitative structure-activity relationship (QSAR) analysis and computer modeling, which can help to identify potential bioactive peptides.
The formation of peptide bonds allows living organisms to create long chains of amino acids known as proteins. These long proteins serve many important functions including providing structural support, catalyzing vital reactions and recognizing molecules in the environment.
To form a peptide bond, the amine group of one amino acid reacts with the carboxyl group of another amino acid in a dehydration reaction. In this process, water is eliminated and a nitrogen atom is substituted for the hydrogen in a covalent bond (shown below). This forms the peptide linkage. The resulting chain is known as a polypeptide.
Polypeptides are used to form larger protein structures such as enzymes, hormones and antibodies. They are also used in the manufacture of cosmetics and anti-ageing creams as they have several benefits such as promoting skin health, stimulating collagen production and protecting against UV damage.
The peptide bond has a very rigid structure due to the fact that atoms C, H and O are approximately co-planar. This rigidity limits the degrees of freedom a polypeptide can have during folding. As a result, peptide bonds are nearly always found in the trans configuration rather than the cis configuration.
Peptides are the precursors of proteins which play many roles in the body, such as hormones and growth factors, and act as antioxidants by scavenging free radicals. They are also involved in cellular signaling and can function as antibodies that recognize antigens and destroy them.
C-peptide is a key insulin secretory hormone and is measured in patients with type 1 diabetes mellitus to determine the reserve of beta-pancreatic cells. Ideally, the value of stimulated C-peptide should be higher than 0.2 nmol/L in order to have good glycemic control and avoid micro-vascular complications.
Neuropeptide B is a peptide hormone that is secreted by various tissues in the body and has a number of biological actions, including appetite suppression, pain inhibition, stress hormone secretion and ovulation. It is also thought to have a role in regulating lipid metabolism and increasing blood flow in the kidneys, muscles, liver and heart. Lastly, neuropeptide B is a potent inducer of brown adipose tissue (BAT) proliferation and mitochondrial function.