Chemical chaperone

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Chemical chaperones are exogenous substances that support the process of protein folding in the endoplasmic reticulum of a cell . They stabilize the protein - conformation against thermally and chemically induced denaturation .

description

Natural chaperones are cellular proteins that "help" newly synthesized proteins to fold correctly. In contrast to this, chemical chaperones are substances supplied from the outside, sometimes with a very simple chemical structure. The chemical chaperones also support the process of protein folding. For example, they increase the solubility of proteins and thus suppress the aggregation of unfolded proteins. Phenylbutyrate (PBA) has a slightly different mechanism of action , which masks the hydrophobic domains of misfolded proteins and thus prevents their aggregation.

For pharmacological in vivo applications as medicaments , systemic concentrations of chemical chaperones that are too high are required, which are associated with considerable toxic side effects . In vitro , on the other hand, chemical chaperones are often used in the production of recombinant proteins . There they increase the production yield.

In contrast to the chemical chaperones, the pharmacological chaperones bind specifically to unfolded proteins - ideally only to one type of protein - and stabilize the structure of the protein. In some publications, however, the terms chemical chaperone and pharmacological chaperone are used synonymously .

Examples

A large number of organic compounds belong to the chemical chaperones. Dimethyl sulfoxide , polyamines such as spermine and spermidine , polyols such as glycerine , and certain amino acids such as lysine are the simplest representatives of chemical chaperones. Phenylbutyrate (more precisely: 4-phenylbutyrate) is a chemical chaperone that has a high pharmacological potential due to its broad spectrum of activity - not only as a chemical chaperone.

further reading

  • E. Papp, P. Csermely: Chemical chaperones: mechanisms of action and potential use. In: Handbook of experimental pharmacology. Number 172, 2006, pp. 405-416, ISSN  0171-2004 . PMID 16610368 .
  • SH Kim, YB Yan, HM Zhou: Role of osmolytes as chemical chaperones during the refolding of aminoacylase. In: Biochemistry and cell biology = Biochimie et biologie cellulaire. Volume 84, Number 1, February 2006, pp. 30-38, ISSN  0829-8211 . doi : 10.1139 / o05-148 . PMID 16462887 .
  • Y. Nagao, H. Ishiguro, N. Nukina: DMSO and glycerol reduce bacterial death induced by expression of truncated N-terminal huntingtin with expanded polyglutamine tracts. In: Biochimica et biophysica acta . Volume 1502, Number 2, October 2000, pp. 247-256, ISSN  0006-3002 . PMID 11040449 .
  • DS Yang, CM Yip et al. a .: Manipulating the amyloid-beta aggregation pathway with chemical chaperones. In: The Journal of biological chemistry . Volume 274, Number 46, November 1999, pp. 32970-32974, ISSN  0021-9258 . PMID 10551864 .

Individual evidence

  1. ↑ a b S. Vogelbein: The quality control system in post-ER compartments of eukaryotic cells using the example of the vasopressin V2 receptor. Dissertation, FU Berlin 2009, p. 21.
  2. ↑ S. Prasad, PB Khadatare, I. Roy: Effect of chemical chaperones in Improving the solubility of recombinant protein in Escherichia coli. In: Applied and environmental microbiology. Volume 77, Number 13, July 2011, pp. 4603-4609, ISSN  1098-5336 . doi : 10.1128 / AEM.05259-11 . PMID 21551288 . PMC 3127727 (free full text).
  3. ^ A. de Marco: Molecular and chemical chaperones for improving the yields of soluble recombinant proteins. In: Methods in molecular biology (Clifton, NJ). Volume 705, 2011, pp. 31-51, ISSN  1940-6029 . doi : 10.1007 / 978-1-61737-967-3_3 . PMID 21125379 . (Review).
  4. ↑ T. Arakawa, Y. Kita et al. a .: Aggregation suppression of proteins by arginine during thermal unfolding. In: Protein and peptide letters. Volume 13, Number 9, 2006, pp. 921-927, ISSN  0929-8665 . PMID 17100648 .
  5. ↑ Y. Suzuki, S. Ogawa, Y. Sakakibara: Chaperone therapy for neuronopathic lysosomal diseases: competitive inhibitors as chemical chaperones for enhancement of mutant enzyme activities. In: Perspectives in medicinal chemistry. Volume 3, 2009, pp. 7-19, ISSN  1177-391X . PMID 19812739 . PMC 2754921 (free full text).
  6. ↑ SZ Bathaie, BB Nobakht u. a .: Effect of chemical chaperones on glucose-induced lysozyme modifications. In: The protein journal. Volume 30, Number 7, October 2011, pp. 480-489, ISSN  1875-8355 . doi : 10.1007 / s10930-011-9353-x . PMID 21882049 .
  7. ↑ T. Iannitti, B. Palmieri: Clinical and experimental applications of sodium phenylbutyrate. In: Drugs in R&D. Volume 11, Number 3, September 2011, pp. 227-249, ISSN  1179-6901 . PMID 21902286 .
  8. ↑ GH Yam, K. Gaplovska-Kysela u. a .: Sodium 4-phenylbutyrate acts as a chemical chaperone on misfolded myocilin to rescue cells from endoplasmic reticulum stress and apoptosis. In: Investigative ophthalmology & visual science. Volume 48, Number 4, April 2007, pp. 1683-1690, ISSN  0146-0404 . doi : 10.1167 / iovs.06-0943 . PMID 17389500 .