Inhibition mechanism of human galectin-7 by a novel galactose- benzylphosphate inhibitor
(2012) In The FEBS Journal 279(2). 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... (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 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2221061
- author
- Masuyer, Geoffrey ; Jabeen, Talat ; Öberg, Christopher T. LU ; Leffler, Hakon LU ; Nilsson, Ulf J. LU and Acharya, K. Ravi
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- drug design, galactoside inhibitor, galectin-7, lectin
- in
- The FEBS Journal
- volume
- 279
- issue
- 2
- pages
- 10 pages
- 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
- 2016-04-04 09:11:36
- date last changed
- 2023-05-15 08:25:22
@article{bc00287a-82cb-46e3-9346-2980d7beb0ef, abstract = {{Galectins are involved in many cellular processes due to their ability <br> to bind carbohydrates. Understanding their functions has shown the <br> necessity for potent and specific galectin inhibitors. Human galectin-7 <br> (hGal-7), in particular, has been highlighted as an important marker in <br> many types of cancer by either inhibiting or promoting tumour growth. <br> Producing ligands able to selectively target hGal-7 will offer promising<br> tools for deciphering cancer processes in which hGal-7 is involved as <br> well as present potential solutions for future therapeutics. Here we <br> report the high resolution crystal structure of hGal-7 in complex with a<br> synthetic 2-<i>O</i>-benzylphosphate-galactoside inhibitor (which is <br> > 60-fold more potent than its parent galactoside). The high <br> resolution crystallographic analysis highlights the validity of using <br> saccharide derivatives, conserving properties of the galactose binding, <br> while enhanced affinity and specificity is provided by the added <br> phosphate group. This structural information will allow the design of <br> further inhibitors with improved potency and specificity.}}, author = {{Masuyer, Geoffrey and Jabeen, Talat and Öberg, Christopher T. and Leffler, Hakon and Nilsson, Ulf J. and Acharya, K. Ravi}}, issn = {{1742-464X}}, keywords = {{drug design; galactoside inhibitor; galectin-7; lectin}}, language = {{eng}}, number = {{2}}, pages = {{193--202}}, publisher = {{Wiley-Blackwell}}, 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}}, doi = {{10.1111/j.1742-4658.2011.08414.x}}, volume = {{279}}, year = {{2012}}, }