Inhibition mechanism of human galectin-7 by a novel galactose- benzylphosphate inhibitor
Author
Summary, in English
Galectins are involved in many cellular processes due to their ability
to bind carbohydrates. Understanding their functions has shown the
necessity for potent and specific galectin inhibitors. Human galectin-7
(hGal-7), in particular, has been highlighted as an important marker in
many types of cancer by either inhibiting or promoting tumour growth.
Producing ligands able to selectively target hGal-7 will offer promising
tools for deciphering cancer processes in which hGal-7 is involved as
well as present potential solutions for future therapeutics. Here we
report the high resolution crystal structure of hGal-7 in complex with a
synthetic 2-O-benzylphosphate-galactoside inhibitor (which is
> 60-fold more potent than its parent galactoside). The high
resolution crystallographic analysis highlights the validity of using
saccharide derivatives, conserving properties of the galactose binding,
while enhanced affinity and specificity is provided by the added
phosphate group. This structural information will allow the design of
further inhibitors with improved potency and specificity.
to bind carbohydrates. Understanding their functions has shown the
necessity for potent and specific galectin inhibitors. Human galectin-7
(hGal-7), in particular, has been highlighted as an important marker in
many types of cancer by either inhibiting or promoting tumour growth.
Producing ligands able to selectively target hGal-7 will offer promising
tools for deciphering cancer processes in which hGal-7 is involved as
well as present potential solutions for future therapeutics. Here we
report the high resolution crystal structure of hGal-7 in complex with a
synthetic 2-O-benzylphosphate-galactoside inhibitor (which is
> 60-fold more potent than its parent galactoside). The high
resolution crystallographic analysis highlights the validity of using
saccharide derivatives, conserving properties of the galactose binding,
while enhanced affinity and specificity is provided by the added
phosphate group. This structural information will allow the design of
further inhibitors with improved potency and specificity.
Department/s
- Centre for Analysis and Synthesis
- Division of Microbiology, Immunology and Glycobiology - MIG
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2012
Language
English
Pages
193-202
Publication/Series
The FEBS Journal
Volume
279
Issue
2
Links
Document type
Journal article
Publisher
Wiley-Blackwell
Topic
- Biochemistry and Molecular Biology
Keywords
- drug design
- galactoside inhibitor
- galectin-7
- lectin
Status
Published
ISBN/ISSN/Other
- ISSN: 1742-464X