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From Structure to Therapy?

  • L. N. Johnson

Abstract

Protein crystal structure determinations have made important contributions to understanding the molecular basis of recognition and function. In some selected examples, protein structures have been used to design new therapeutic agents. This paper summarises recent achievements and reports on progress in our long term study to provide potential agents for the treatment of diabetes. Structural studies with glycogen phosphorylase have led to the design of a series of glucose analogue inhibitors that can act as powerful regulators of liver glycogen metabolism. The best compound to date has involved some novel carbohydrate chemistry and exhibits a Ki that is 3 orders of magnitude lower than that of glucose. Physiological studies have shown that inhibitors more potent than glucose produce dramatic effects in inhibition of glycogen degradation and promotion of increased glucose utilisation and glycogen deposits in isolated hepatocytes.

Keywords

Glycogen Phosphorylase Glycogen Metabolism Purine Nucleoside Phosphorylase Structure Base Drug Design Glycogen Degradation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • L. N. Johnson
    • 1
  1. 1.Laboratory of Molecular BiophysicsUniversity of OxfordOxfordUK

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