Advanced

Inhibition mechanism of human galectin-7 by a novel galactose-benzylphosphate inhibitor.

Masuyer, Geoffrey; Jabeen, Talat; Oberg, Christopher T; Leffler, Hakon LU ; Nilsson, Ulf J and Acharya, K Ravi (2012) In The FEBS Journal 279. p.193-202
Abstract
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 potent than its parent galactoside).... (More)
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 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 inhibitor with improved potency and specificity. Structured digital abstract hGal-7 and hGal-7 bind by x-ray crystallography (View interaction). (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The FEBS Journal
volume
279
pages
193 - 202
publisher
Wiley-Blackwell
external identifiers
  • WOS:000298746000001
  • PMID:22059385
  • Scopus:84855457490
ISSN
1742-464X
DOI
10.1111/j.1742-4658.2011.08414.x
language
English
LU publication?
yes
id
bc00287a-82cb-46e3-9346-2980d7beb0ef (old id 2221061)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22059385?dopt=Abstract
date added to LUP
2011-12-02 19:42:57
date last changed
2016-11-09 15:36:49
@misc{bc00287a-82cb-46e3-9346-2980d7beb0ef,
  abstract     = {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 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 inhibitor with improved potency and specificity. Structured digital abstract hGal-7 and hGal-7 bind by x-ray crystallography (View interaction).},
  author       = {Masuyer, Geoffrey and Jabeen, Talat and Oberg, Christopher T and Leffler, Hakon and Nilsson, Ulf J and Acharya, K Ravi},
  issn         = {1742-464X},
  language     = {eng},
  pages        = {193--202},
  publisher    = {ARRAY(0xb781580)},
  series       = {The FEBS Journal},
  title        = {Inhibition mechanism of human galectin-7 by a novel galactose-benzylphosphate inhibitor.},
  url          = {http://dx.doi.org/10.1111/j.1742-4658.2011.08414.x},
  volume       = {279},
  year         = {2012},
}