peptide

A peptide is an organic compound that contains peptide bonds between amino acids . Oligopeptides with few amino acids are differentiated from polypeptides with many amino acids according to their number . Long polypeptide chains are also referred to as proteins , especially those formed by protein biosynthesis .

properties

Peptides in which individual amino acids are linked linearly to a chain in a defined order ( sequence ) can be regarded as a small protein . Peptides with circularly bound amino acids are called cyclopeptides . Peptides also differ mainly in their molar mass . The distinction to proteins according to the number of linked amino acids is fluid; a chain of more than about 100 linked amino acids that folds into a specific shape 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 only form peptides by translation from α-amino acids of the L -form, because only the genetically coded amino acids that are bound to a tRNA are available for this process . Chance of different creatures are found in rich and D -amino acids in peptides, however, these are products of specific metabolic pathways of a non- ribosomal peptide synthesis and not the protein biosynthesis . Peptides fulfill a large number of physiological functions and can, for example, act as hormones , while others show anti-inflammatory or pro-inflammatory 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 the peptone (from Greek πεπτικός peptikos , digestible 'or πεπτός peptos ' cooked'), understood as being made up of monomers , analogous to a polysaccharide .

structure

Mesomeric boundary structures of a simple peptide bond in a dipeptide composed of alanine (here N term ) and glycine (here C term ) with the corresponding cis or trans configuration

A tetrapeptide - here for example Val - Gly - Ser - Ala with a green marked N-terminal α-amino acid residue (in the example: L -Valin ) and a blue marked C-terminal α-amino acid residue (in the example: L -alanine ) - is made up of four amino acids

Oxytocin is a nonapeptide . Nerve cells in the hypothalamus use a precursor protein (106 amino acids) to form this oligopeptide as a messenger substance and also release the neuropeptide in the (neuro-) pituitary gland so that it acts as a neurohormone .

During the condensation of amino acids, the carboxy group of one amino acid formally reacts with the amino group of the other amino acid to form the acid amide group -CO-NH- with elimination of water , and the newly made amide bond between the carbon atom of the carbonyl group and the nitrogen atom becomes a peptide bond . The free amino group at one end of the peptide is called the N terminus , and the free carboxy group at the other end is called the C terminus .

The N -terminal end is conventionally written on the left, the C -terminal end on the right. With the exception of the C -terminal amino acid, all amino acids on the left have the ending -yl in their trivial names, only the name of the amino acid on the right does not change (example: a dipeptide made up of two alanine amino acids is called alanyl-alanine).

The peptide bond is not freely rotatable because there are two resonance structures. This plays an important role in the structure of proteins.

Classification

In general, peptides are differentiated according to the number of amino acids that make up a peptide molecule. The number of possible combinations increases exponentially, to the base 20 when restricted to the 20 canonical amino acids of protein biosynthesis.

designation	n number of amino acids	20 n possible combinations
Dipeptides	2	400
Tripeptides	3	8,000
Tetrapeptides	4th	160,000
Pentapeptides	5	3,200,000
Hexapeptides	6th	64,000,000
Heptapeptides	7th	1,280,000,000
Octapeptides	8th	25,600,000,000
Nonapeptides	9	512,000,000,000
Oligopeptides	under approx. 10
Polypeptides	over approx. 10
Macropeptides	over approx. 100

In most peptides the linked amino acids form chains; the ends are referred to as N - and C -terminus refers to the number of amino acids as chain length. In cyclopeptides two or more amino acids are annularly connected to one another.

Proteins mostly consist of polypeptide chains of over a hundred amino acids. Due to protein folding, they have a certain spatial structure that is essential for their biological function and can be stabilized by means of disulfide bridges . Proteins can also aggregate and form a protein complex , such as hemoglobins .

Oligopeptides

Oligopeptides are chemical compounds that consist of up to ten amino acids that are linked to one another via peptide bonds .

An oligopeptide is formed when the amino group of a first amino acid reacts with the carboxy group of a second amino acid with elimination of water . The free amino group of the resulting dipeptide then reacts with the carboxy group of another amino acid. Further amino acids can be linked according to this pattern, so that a short chain of amino acids is created that are connected to one another via peptide bonds. If the two chain ends are also linked together, a cyclic peptide is created (see below ).

Oligopeptides play e.g. B. as components of enzymes a role in detoxification, transport and metabolic processes .

Polypeptides

A polypeptide is a peptide that consists of at least ten amino acids linked by peptide bonds . Polypeptides can be of either natural or synthetic origin. Polypeptide chains with more than 100 amino acids are usually referred to as proteins ; however, other prerequisites are necessary for a protein, such as a certain protein folding .

Macropeptides are high molecular weight peptides. If these are linked 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.

Cyclopeptides

In cyclic dipeptides such as 2,5-diketopiperazines (left) made from glycine and L - alanine (left) or cyclodi- L -prolyl (right), formed from two L - proline molecules, two amino acids are linked in a ring . The cis peptide bonds are marked blue here .

→ Main article : Cyclopeptides

Cyclic peptides consist of two or more amino acids arranged in a ring. Therefore, cyclopeptides have no C -terminal and no N -terminal amino acid. All cyclic peptides are therefore lactams at the same time . Cis peptide bonds are present in the circular peptides , while trans peptide bonds dominate in most native (chain-shaped) proteins . 2,5- Diketopiperazines are the simplest cyclic dipeptides. Some antibiotics are cyclopeptides, e.g. B. Ciclosporin .

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

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

Glutathione (γ- L -glutamyl- L -cysteine ​​glycine) is a tripeptide with a γ-peptide bond (= example of an ω-peptide bond) and an α-peptide bond .

However, there are also α-amino acids which contain a second amino group in addition to the α-amino group, e.g. B. L - lysine . There are also α-amino acids which contain a second carboxy group in addition to the α-carboxy group, e.g. B. L - aspartic acid and L - glutamic acid . Now, when the linkage of the amino acids not effected exclusively by the α-position amino and carboxy groups, but with the involvement of a terminal or pendant diamino (such as L -lysine) and amino dicarboxylic acids (such as L -aspartic acid and L -glutamic acid) as occur with peptides an ω-peptide bond.

N ^ε -γ- L -glutamyl- L -lysine contains an isopeptide bond .

Mixed forms also occur in nature, for example the tripeptide glutathione (γ- L -glutamyl- L -cysteine ​​glycine) contains one α-peptide bond and one ω-peptide bond. The peptide bond between the pendant ε-amino group of L- lysine and the pendant carboxy group of aspartic acid or glutamic acid is also called an isopeptide bond .

Peptide synthesis

Ribosomal Peptide Synthesis

→ Main article : Protein synthesis

In the cells of living things, individual polypeptide chains are built up on the ribosomes , which then unfold to form proteins . This ribomosomal peptide synthesis is also called protein biosynthesis.

Non-ribosomal peptide synthesis

In addition, in some organisms there is also a non-ribosomal peptide synthesis in a purely enzymatic way using non-ribosomal peptide synthetases ( NRPS ). D- amino acids can also be incorporated through NRPS or cyclopeptides are formed as non-ribosomal peptides (NRP). Such NRPS occur 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 in some molluscs .

Technical-chemical peptide synthesis

→ Main article : 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

If an attempt is made to produce a certain dipeptide (e.g. Gly-Val) from two different amino acids (Gly + Val) by thermal dehydration, a number of undesirable products arise in considerable quantities:

${\displaystyle \mathrm {\ Gly+Val\rightarrow Gly{-}Gly\ +\ Gly{-}Val\ +\ Val{-}Gly\ +\ Val{-}Val\ +\ Gly{-}Val{-}Val\ +} }$ ${\displaystyle \mathrm {\ Val{-}Val{-}Gly\ +\dots } }$

In order to increase the selectivity , the carboxy and amino groups that are not to be linked are provided with a protective group (e.g. ester, Boc , Fmoc ).

Various coupling reagents are used which activate the unprotected carboxy group of one amino acid and thus enable the linkage with the amino function of the second amino acid under mild conditions. There are different classes of such coupling reagents:

• Phosphonium reagents (e.g. BOP , PyBOP )
• Uronium reagents (e.g. HBTU , HATU , TBTU )
• Immonium reagents
• Carbodiimide reagents (e.g. DCC , EDC )
• Imidazolium reagents (e.g. CDI )
• Organophosphorous reagents
• Acid halogenating reagents
• Chloroformates and others

After the peptide bond has been made in this way, one of the two protective groups is selectively removed. It can then be coupled again with a further appropriately protected amino acid, etc. At the end, all protective groups are removed and the desired peptide is isolated.

The synthesis can take place in the liquid phase or as a solid phase synthesis . In addition, enzymes can also be used for peptide synthesis .

See also

• Pepzyme
• Peptide nucleic acid (PNA)

literature

• S. Donadio, P. Monciardini, M. Sosio: Polyketide synthases and nonribosomal peptide synthetases: the emerging view from bacterial genomics. In: Natural Product Reports Volume 24, Number 5, October 2007, pp. 1073-1109. doi: 10.1039 / b514050c . PMID 17898898 .

Web links

• Peptides Guide

Individual evidence

1. ↑ In the smallest possible peptide, a dipeptide made up of two amino acids, there is only one peptide bond.
2. ↑ Hans-Dieter Jakubke, Hans Jeschkeit: amino acids, peptides, proteins , Verlag Chemie, Weinheim, 1-505, 1982, ISBN 3-527-25892-2 .
3. ↑ G. Kreil: D-amino acids in animal peptides . In: Annual Review of Biochemistry . 66, No. 1, 1997, pp. 337-345. doi : 10.1146 / annurev.biochem.66.1.337 .
4. ↑ E. Fischer: About the hydrolysis of protein substances. In: Chemikerzeitung. Volume 26, 1902, pp. 939-940.
5. ↑ Otto-Albrecht Neumüller (Ed.): Römpps Chemie-Lexikon. Volume 4: M-Pk. 8th revised and expanded edition. Franckh'sche Verlagshandlung, Stuttgart 1985, ISBN 3-440-04514-5 , p. 2894.
6. ↑ Biologically active peptides. Script of the University of Leipzig, p. 16. (PDF; 3.2 MB).
7. ↑ Hans-Dieter Jakubke, Hans Jeschkeit: amino acids, peptides, proteins , Verlag Chemie, Weinheim, p 99, 1982, ISBN 3-527-25892-2 .
8. ↑ Hans-Dieter Jakubke, Hans Jeschkeit: amino acids, peptides, proteins , Verlag Chemie, Weinheim, p 99, 1982, ISBN 3-527-25892-2 .
9. ↑ Otto-Albrecht Neumüller (Ed.): Römpps Chemie-Lexikon. Volume 2: Cm-G. 8th revised and expanded edition. Franckh'sche Verlagshandlung, Stuttgart 1981, ISBN 3-440-04512-9 , p. 1511.
10. ↑ Hao Wang, David Fewer, Liisa Holm, Leo Rouhiainen, Kaarina Sivonena: Atlas of nonribosomal peptide and polyketide biosynthetic pathways reveals common occurrence of nonmodular enzymes . In: Proc Natl Acad Sci USA . Volume 111, No. 25, June 2014, pp. 9259-9264. PMC 4078802 (free full text).
11. ↑ Hans-Dieter Jakubke, Hans Jeschkeit: amino acids, peptides, proteins , Verlag Chemie, Weinheim, 107-261, 1982, ISBN 3-527-25892-2 .
12. ↑ KPC Vollhardt, NE Schore: Organic Chemistry , 4th Edition, Wiley-VCH, pp. 1399-1402, 2005.
13. ^ SY Han, YA Kim: Tetrahedron , 60, 2004, pp. 2447-2467.