Allosterická vazebná místa jako molekulární cíle pro vývoj, design a působení nových léčiv

  • H. Farghali Farmakologický ústav, 1. lékařská fakulta Univerzity Karlovy v Praze, Praha
  • N. Kutinová Canová Farmakologický ústav, 1. lékařská fakulta Univerzity Karlovy v Praze, Praha
Klíčová slova: allosterický efekt, allosterické místo, GABA(A) receptorový komplex, kalcimimetika, sirtuin 1

Abstrakt

Widespread occurrence of allostery has been recently exploited for design and development of drugs that bind to physiological or non-physiological allosteric sites. This may lead to gain or loss of function. Allosterism can be exploited in development and design of allosteric drugs. Benzodiazepines are classical examples of allosteric agonists for the GABAA receptor complex, where the neurotransmitter 4-aminobutanoic acid (GABA) binds to the active site and benzodiazepines bind to the regulatory site. The allosteric modulation of the Ca-sensing receptor with important clinical consequences has been described. Some of calcimimetics such as cinacalcet were approved for the treatment of certain forms of hyperparathyroidism. Allosteric modulators of regulatory target proteins such as sirtuin 1 are intensively investigated.

Publikované
2013-07-15
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