Origin of Chiral Pharmacology Stereochemistry in Metalloprotease Inhibition

Author: Kim D.H.

Source: Mini Reviews in Medicinal Chemistry, Volume 1, Number 2, July 2001 , pp. 155-161(7)

Publisher: Bentham Science Publishers

Abstract:

The stereospecificity shown by a wide variety of inhibitors that are effective for carboxypeptidase A (CPA), a representative zinc protease is analyzed on the basis of inhibitor type. In cases of ground state analog inhibitors and transition state analog inhibitors, the stereoisomers having the stereochemistry that corresponds to stereochemistry of substrate are more potent, but in the case of irreversible inhibitors including mechanism-based inactivators the preferred inhibitory stereochemistry cannot be predicted simply from the substrate stereospecificity. The Ogston three point fit concept may be of great value in understanding the inhibitory stereochemistry of reversible competitive inhibitors. On the other hand, the stereochemistry of irreversible inhibitors may possibly be predicted on the ground of the transition state structure that plays a critical role in the inactivation pathway.

Keywords: Metalloprotease Inhibition; carboxypeptidase A (CPA); SUBSTRATE ANALOG INHIBITORS; Thermolysin Inhibitors

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389557013407016

Publication date: 2001-07-01

• The aim of Mini-Reviews in Medicinal Chemistry is to publish short reviews on the important recent developments in medicinal chemistry and allied disciplines.
  
  The scope of Mini-Reviews in Medicinal Chemistry will cover all areas of medicinal chemistry including developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, drug targets, and natural product research and structure-activity relationship studies.
  
  Mini-Reviews in Medicinal Chemistry is an essential journal for every medicinal and pharmaceutical chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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