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

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.