What are Peptides?
A peptide is a molecule created by joining two or more amino acids together. They are present in every living cell and possess a variety of biochemical activities. In general if the number of amino acids is less than fifty, these molecules are called peptides, while larger sequences are referred to as proteins. So peptides can be thought of as tiny proteins that are simply strings of amino acids.
Peptides in which individual amino acids are linearly linked to a chain in a defined order (sequence) can be considered as a small protein. Peptides with circularly bound amino acids are called cyclopeptides. In addition, peptides differ mainly by their molar masses. The delineation to proteins by number of linked amino acids is fluid; With a chain of more than about 100 linked amino acids that unfolds into a particular shape, the molecule is commonly referred to as a protein. Peptides with glycosylations are referred to as glycopeptides or as glycoproteins, peptides with lipids as lipopeptides or as lipoproteins.
Organisms can form peptides by translation exclusively from α-amino acids of the L-form, because for this process only the genetically coded amino acids are available, which are bound to a tRNA. Occasionally, creatures of various kingdoms also contain D-amino acids in peptides, but these are products of special metabolic pathways of nonribosomal peptide synthesis and not of protein biosynthesis. Peptides fulfill a large number of physiological functions and can act as hormones, for example, others have anti-inflammatory or proinflammatory effects; There are also antimicrobial peptides with antibiotic or antiviral effects. In some cases, their mode of action has been well researched.
The term peptide was first used in 1902 by Emil Fischer for the starting materials of the protein degradation products by pepsin in peptone (to Greek πεπτικός peptikos' digestible 'or πεπτός peptos, cooked'), conceived as constructed from monomers, analogous to a polysaccharide.
In the condensation of amino acids, the carboxy group of one amino acid formally reacts with water leaving with the amino group of the other amino acid to the acid amide group -CO-NH-, the newly linked amide bond between the carbon atom of the carbonyl group and the nitrogen becomes a peptide bond. The free amino group at one end of the peptide is called the N-terminus, the free carboxy group at the other end is called the C-terminus.
The peptide bond is not freely rotatable because there are two resonance structures. This plays an important role in the structure of proteins.
By number of amino acids that make up a peptide molecule, peptides are widely differentiated into:
Oligopeptides below approx. 10
Polypeptides over about 10
Macropeptides above approx. 100
For most peptides, the linked amino acids form chains; their ends are called N- and C-terminus, the number of amino acids as chain length. In cyclopeptides, two or more amino acids are connected to each other in a ring.
Proteins usually consist of polypeptide chains of over a hundred amino acids. Through protein folding, they have a specific spatial structure that is essential for their biological function and can be stabilized by means of disulfide bridges. In addition, proteins can assemble and form a protein complex, such as hemoglobins.
Oligopeptides are chemical compounds that consist of up to ten amino acids, which are linked to one another via peptide bonds.
An oligopeptide is formed by dehydration by reacting the amino group of a first amino acid with the carboxy group of a second amino acid. Subsequently, the free amino group of the resulting dipeptide reacts with the carboxy group of another amino acid. Following this pattern, additional amino acids can be attached, resulting in a short chain of amino acids linked by peptide bonds. If the two chain ends are also linked, a cyclic peptide is formed (see below).
Oligopeptide play z. B. as components of enzymes in detoxification, transport and metabolic processes a role.
A polypeptide is a peptide consisting of at least ten amino acids linked by peptide bonds. Polypeptides may be of both natural and synthetic origin. Polypeptide chains with over 100 amino acids are usually referred to as proteins; however, for a protein further conditions are necessary, such as a certain protein folding.
Macropeptides are high molecular weight peptides. If these are connected by hydrogen or disulfide bridges, one often speaks of proteins. However, some amino acid chains with more than 100 amino acids are only referred to as peptides.
Ribosomal Peptide Synthesis
→ Main article: Protein biosynthesis
In the cells of living organisms, individual polypeptide chains are built up on the ribosomes, which then unfold into protein. This ribomosomal peptide synthesis is also called protein biosynthesis.
Nonribosomal Peptide Synthesis
In addition, some organisms also have non-ribosomal peptide synthesis by purely enzymatic means using nonribosomal peptide synthetases (NRPS). NRPS can also be used to incorporate D-amino acids or cyclopeptides are formed as nonribosomal peptide (NRP). Such NRPS are found not only in various microorganisms of the three domains of bacteria, archaea and eukaryotes, but also, for example, in multicellular organisms of many fungi and some mollusks.
Technical-chemical peptide synthesis
The technical-chemical synthesis method of choice for a peptide of a certain sequence differs depending on its length:
Short peptides are built up step by step from the linkage of amino acids
Longer peptides are built from the linkage of shorter peptides
To increase the selectivity, the carboxy and amino groups which are not to be linked are capped (e.g., esters, Boc, Fmoc).
Various coupling reagents are used which activate the unprotected carboxy group of one amino acid, thus allowing linkage to the amino function of the second amino acid under mild conditions. There are several classes of such coupling reagents:
Phosphonium reagents (eg BOP, PyBOP)
Uronium reagents (eg HBTU, HATU, TBTU)
Carbodiimide reagents (eg DCC, EDC)
Imidazolium reagents (eg CDI)
Acid halogenating reagents
Chloroformates and others
After the peptide bond has been attached, one of the two protecting groups is selectively removed. Then one can re-couple with another appropriately protected amino acid, etc. Finally, all the protecting groups are removed and the desired peptide is isolated.