Peptide

A peptide, an organic compound containing peptide bonds between amino acids can be considered as a small protein. The individual amino acids are usually connected in a defined order ( sequence) linearly to a chain. Circular arranged peptides are called cyclic peptides.

Peptides differ from proteins mainly by their molar masses, ie by the number of linked amino acids. The distinction is blurred; greater than about 100 amino acids linked the molecule is referred to as protein.

Organisms can form peptides by transcription exclusively of α -amino acids of L-form, as for this process, only the genetically encoded amino acids, and in all known exceptions to the genetic code, is available. With representatives of all kingdoms can be found sporadically and D- amino acids in peptides, these are products of specific metabolic pathways and not the protein. Peptides meet a large number of physiological functions. Their mode of action is well understood in many cases. Peptides can act as hormones, show anti-inflammatory or other pro-inflammatory effects, it is antimicrobial and antiviral effects.

Some proteins frequently occurring in the diet such as gluten, casein or egg or spinach in existing proteins ( = German name for " proteins ") can be converted by the digestive processes into so-called opioid peptides. These peptides act in a manner similar to morphine on the body. People who are not able to metabolize these peptides further can develop signs of physical and mental disease.

The term peptide was first coined in 1902 by Emil Fischer at the 74th Annual Meeting of German Natural Scientists and Physicians in Carlsbad. Peptide results ( = Greek peptos digested ') from peptone, protein breakdown products of pepsin, and the ending of polysaccharide, because of the analogy to its structure of monomers.

• 3.1 Ribosomal Peptide Synthesis
• 3.2 Nonribosomal peptide synthesis ( NRPS )
• 3.3 Technical and chemical peptide synthesis

Structure

In the condensation of amino acids the carboxyl group of one amino acid reacts formal elimination of water with the amino group of another amino acid to Säureamidgruppierung -CO -NH-, the newly formed amide bond between the carbon atom of the carbonyl group and the nitrogen atom is a peptide bond. The free amino group at one end of the peptide is known as N-terminus, the free carboxyl group at the other end is called the C-terminus.

The peptide bond can not rotate freely, as there are two resonance structures. This plays an important role in the structure of proteins.

Classification

Generally the number of amino acids constituting a peptide molecule, referred to as chain length. Based on the chain length is differentiated into:

Oligopeptides

Oligopeptides as chemical compounds are referred to, consisting of up to ten amino acids, which are linked to one another via peptide bonds.

An oligopeptide is formed by reacting the amino group of a first amino acid with the carboxyl group of a second amino acid with the elimination of water. Then the free amino group of the resulting dipeptide reacts with the carboxyl group of another amino acid. According to this pattern, the remaining amino acids are linked, so that a short chain of amino acids is formed, which are connected to one another via peptide bonds.

Oligopeptides play a role, for example as components of enzymes in detoxification, transport and metabolic processes.

Polypeptides

A polypeptide is a peptide that consists of at least ten amino acids. The amino acids are linked by peptide bonds. Polypeptides may be of both natural and synthetic origin. Polypeptides with more than 100 amino acids are typically referred to as proteins; However, further requirements are necessary for a protein, such as a defined protein folding.

Are high molecular weight macro peptides linked by hydrogen or disulfide bonds, called these proteins. Depending on the historical classification of some amino acids chains with more than 100 amino acids are called peptides.

Cyclopeptides

Cyclic peptides containing two, three or more amino acids that form rings; therefore cyclopeptides do not have C-terminal and N- terminal amino acid no more. All cyclic peptides are thus at the same time lactams. In the annular peptides are cis peptide bonds, whereas dominate in most native ( chain-like ) proteins trans peptide bonds. 2,5 - diketopiperazines are the simplest cyclic dipeptides. Some antibiotics are cyclic peptides, such as ciclosporin.

Peptides with α - peptide bonds and ω - peptide bonds and isopeptides

Strictly speaking, arise peptides by linking α - amino and carboxy groups of constant α - amino acids are then linked by α - peptide bonds.

However, there are α -amino acids which contain a second amino group in addition to the α -amino group, for example, L -lysine. Similarly, there are α -amino acids, which in addition to the α - carboxyl group of a second carboxyl group, e.g., L- aspartic acid and L -glutamic acid. Now, if the linkage of amino acids not only by the α -position amino and carboxy groups, but with the involvement of a terminal or pendent diaminocarboxylic ( such as L- lysine ) and amino dicarboxylic acids ( such as L- aspartic acid and L- glutamic acid) so develop peptides with an ω - peptide bond.

In nature, mixed forms occur, as the tripeptide glutathione ( γ -L- glutamyl -L- cysteinglycin ) contains one α - peptide bond and an ω - peptide bond. The peptide bond between the ε -amino group pendent of L -lysine and the pendant carboxyl group of aspartic acid or glutamic acid is also called isopeptide bond.

Peptide synthesis

Ribosomal Peptide Synthesis

In the living nature (biology) the synthesis of individual polypeptide chains is effected by ribosomes.

Nonribosomal peptide synthesis ( NRPS )

There is also a nonribosomal peptide synthesis ( NRPS ), purely enzymatic way (by means of peptide synthetases ). Means NRPS and D -amino acids may be incorporated or cyclopeptides arise. NRPS is common for microorganisms (bacteria and fungi), but is probably in all organisms ( Drosophila, to mice )

Technical and chemical peptide synthesis

The technical- chemical synthesis method of choice for a certain peptide sequence differs depending on its length:

• Short peptides are built up gradually from the linking of amino acids
• Longer peptides are assembled from the combination of shorter peptides

An attempt is made to produce a specific dipeptide by thermal dehydration (e.g., Gly -Val ) of two different amino acids (Gly Val ), create a number of undesirable products in significant quantity:

In order to increase the selectivity, the carboxyl and amino groups, which are not to be linked, provided with a protective group (eg, ester, Boc, Fmoc).

Various coupling agents are used to activate the carboxy group of an unprotected amino acid, enabling the linkage to the amino function of the second amino acid under mild conditions which. There are several classes of such coupling reagents:

• Phosphonium reagents (eg, BOP, PyBOP )
• Uronium reagents (eg HBTU, HATU )
• Immonium reagents
• Carbodiimide reagents (eg, DCC, EDC)
• Imidazolium reagents (e.g., CDI)
• Organophosphorige reagents
• Chloroformates and other

After the peptide bond has been linked as one of the two protecting groups is selectively removed. Then it can be coupled again with another appropriately protected amino acid, etc. In the end, all protecting groups are removed, and isolating the desired peptide.

Alternatively, solid-phase syntheses are used today mostly. In addition, enzymes may be used for peptide synthesis.