Cyclopeptides

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Cyclotriprolyl is a cyclic tripeptide made up of three residues of the amino acid L - proline .

Cyclopeptides (synonymous cyclic peptides ) are ring-shaped peptides and thus lactams at the same time .

properties

The cyclopeptides include oligo- and polypeptides whose amino acid sequence is covalently closed to form a ring or several. As so-called homo finished cyclopeptides they have peptide bonds between all amino acids, such as cyclosporin A .

By contrast, heterogeneous cyclopeptides also have other than just peptide bonds, for example bacitracin and microcystin each have an isopeptide bond in addition . The cyclopeptides of the amatoxins and phallotoxins have, in addition to the ring-shaped peptide bonds between their amino acids, an internal cross bridge between tryptophan and cysteine ​​(as tryptathionine ). Aureobasidin A and HUN-7293 also have ester bonds .

Cyclopeptides with two rings are called bicyclic peptides, and the smallest are phalloidin and amanitin .

Further examples of cyclopeptides are bacitracin , colistin , Cyclotid , dactinomycin , daptomycin , gramicidin S , HC-toxin , hymenistatin , nisin , polymyxin B , pristinamycin , octreotide , valinomycin , Viscumamid or Yunnanin A .

Due to the ring shape, cyclopeptides are often resistant to proteolysis (e.g. by exopeptidases ), have a higher thermal stability and are less mobile.

The definition of heterodyne cyclopeptides also includes chain-like peptides (e.g. keratin , insulin , oxytocin ) in which two or more chains are connected to one another via several disulfide bridges - these peptides also contain rings, but are not included in the narrower sense Cyclopeptides.

Cyclopeptides serve a variety of different functions in nature. Often cyclopeptides containing rather than the usual L - amino acids partly D -amino acids or α- hydroxy carboxylic acids ( cyclodepsipeptides ). The cyclodepsipeptides are both lactams and lactones . Some cyclopeptides are produced by non-ribosomal peptide synthesis .

Examples

Cyclopeptides (examples)
Surname Cyclodipeptide Gly-Gly Cyclodipeptide Ala-Ala Cyclodepsipeptide
Structural formula Cyclic dipeptide Gly-Gly, the simplest diketopiperazine, made up of two molecules of glycine Cyclic dipeptide Ala-Ala, a diketopiperazine made up of two alanine molecules Cyclic depsipeptide, made up of glycine and the hydroxycarboxylic acid L-lactic acid.
comment Simplest diketopiperazine, composed of two molecules of glycine (peptide bonds marked in blue ) A diketopiperazine made up of two alanine molecules (peptide bonds marked in blue ) Cyclic depsipeptide, made up of glycine and the hydroxycarboxylic acid L - lactic acid (peptide bond marked in blue )

The simplest cyclic peptides are diketopiperazines (cyclic dipeptides ). Examples of larger homodete cyclopeptides are caspofungin , octreotide and gramicidin  S, whereas the cyclopeptides oxytocin , daptomycin and α- amanitin are heterodetate. Further examples of cyclopeptides are penicillin , vancomycin , echinocandins and bleomycin .

application

In the course of protein design , cyclic fusion proteins can be generated which, due to the lack of access for exopeptidases, have a higher stability (and thus a longer biological half-life ) or activity. Isopeptidic cyclopeptides can be generated by ineins in vivo .

Individual evidence

  1. ↑ M. Rothe, K.-D. Steffen, I. Rothe: Synthesis of cyclo-tri-L-prolyl, a cyclo-tri-peptide with a nine-membered ring, Angewandte Chemie 77, 1965, pp. 347-348.
  2. ↑ 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. 847.
  3. ^ DJ Craik: Chemistry. Seamless proteins tie up their loose ends. In: Science . Volume 311, number 5767, March 2006, pp. 1563–1564, doi : 10.1126 / science.1125248 . PMID 16543448 .
  4. ^ SH Joo: Cyclic peptides as therapeutic agents and biochemical tools. In: Biomolecules & Therapeutics . Volume 20, number 1, January 2012, pp. 19-26, doi : 10.4062 / biomolther.2012.20.1.019 . PMID 24116270 . PMC 3792197 (free full text).
  5. ↑ K. Sivonen, N. Leikoski, DP Fewer, J. Jokela: Cyanobactins-ribosomal cyclic peptides produced by cyanobacteria. In: Applied Microbiology and Biotechnology . Volume 86, Number 5, May 2010, pp. 1213-1225, doi : 10.1007 / s00253-010-2482-x . PMID 20195859 . PMC 2854353 (free full text).
  6. ↑ A. Jegorov, M. Hajduch, M. Sulc, V. Havlicek: Nonribosomal cyclic peptides: specific markers of fungal infections. In: Journal of Mass Spectrometry Volume 41, Number 5, May 2006, pp. 563-576, doi : 10.1002 / jms.1042 . PMID 16770826 .
  7. ↑ M. Katsara, T. Tselios, S. Deraos, G. Deraos, MT Matsoukas, E. Lazoura, J. Matsoukas, V. Apostolopoulos: Round and round we go: cyclic peptides in disease. In: Current Medicinal Chemistry . Volume 13, Number 19, 2006, pp. 2221-2232, PMID 16918350 .
  8. ↑ S. Chen, R. Gopalakrishnan, T. Schaer, F. Marger, R. Hovius, D. Bertrand, F. Pojer, C. Heinis: Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides. In: Nature Chemistry . Volume 6, number 11, November 2014, pp. 1009-1016, doi : 10.1038 / nchem.2043 . PMID 25343607 .
  9. ↑ M. Cemazar, S. Kwon, T. Mahatmanto, AS Ravipati, DJ Craik: Discovery and applications of disulfide-rich cyclic peptides. In: Current Topics in Medicinal Chemistry . Volume 12, Number 14, 2012, pp. 1534-1545, PMID 22827522 .
  10. ↑ AR Horswill, SJ Benkovic: Cyclic peptides, a chemical genetics tool for biologists. In: Cell cycle (Georgetown, Tex.). Volume 4, Number 4, April 2005, pp. 552-555, PMID 15876867 .