Disease-associated carbohydrate-recognising proteins and structure-based inhibitor design

Curr Opin Struct Biol. 2008 Oct;18(5):558-66. doi: 10.1016/j.sbi.2008.07.006. Epub 2008 Sep 3.

Abstract

The role of carbohydrate-related pathways in a wide range of clinically significant diseases has provided great impetus for researchers to characterise key proteins as targets for drug discovery. Carbohydrate-recognising proteins essential in the lifecycles of high health impact pathogens and diseases such as diabetes, cancer, autoimmunity, inflammation and in-born errors of metabolism continue to stimulate much interest in both structure elucidation and structure-based drug design. For example, advances in structure-based inhibitor design against the mycobacterial enzyme UDP-galactopyranose mutase offer new hope in next generation anti-tuberculosis chemotherapeutics. The appearance of H5N1 avian influenza virus has re-stimulated much research on influenza virus haemagglutinin and sialidase. These latest developments on influenza virus sialidase have provided new opportunity for the development of Group 1-specific anti-influenza drugs. The role of siglecs and galectins in a range of disease processes such as inflammation, apoptosis and cancer progression has also inspired significant structure-based inhibitor design research.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / therapeutic use
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / therapeutic use
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / therapeutic use
  • Chagas Disease / drug therapy
  • Drug Design
  • Drug Resistance, Multiple
  • Hemagglutinins / drug effects
  • Humans
  • Intramolecular Transferases
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / enzymology
  • Neuraminidase / antagonists & inhibitors
  • Staphylococcus aureus / drug effects
  • Trypanocidal Agents / chemical synthesis
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / therapeutic use
  • Trypanosoma cruzi / drug effects

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Antiviral Agents
  • Hemagglutinins
  • Trypanocidal Agents
  • Neuraminidase
  • Intramolecular Transferases
  • UDP-galactopyranose mutase