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Taloside inhibitors of Galectin-1 and Galectin-3.

Collins, Patrick M; Oberg, Christopher T; Leffler, Hakon LU ; Nilsson, Ulf J and Blanchard, Helen (2012) In Chemical Biology and Drug Design 79(3). p.339-346
Abstract
Galectin-1 and galectin-3 have roles in cancer and inflammation. Galectin-1 has recently emerged as a significant protein produced by tumour cells to promote tumour development, angiogenesis and metastasis and consequently represents an important target to inhibit. The design of inhibitors targeting the carbohydrate recognition domain that is known to recognise galactose is an important approach in the fight against cancer. Based on analysis of crystal structures, we pursued the concept that if the galactose were to be replaced with talose (the C2 epimer of galactose) as a scaffold, then O2 substituents would be directed closer to the protein surface and provide opportunity to design inhibitors that are more specific toward particular... (More)
Galectin-1 and galectin-3 have roles in cancer and inflammation. Galectin-1 has recently emerged as a significant protein produced by tumour cells to promote tumour development, angiogenesis and metastasis and consequently represents an important target to inhibit. The design of inhibitors targeting the carbohydrate recognition domain that is known to recognise galactose is an important approach in the fight against cancer. Based on analysis of crystal structures, we pursued the concept that if the galactose were to be replaced with talose (the C2 epimer of galactose) as a scaffold, then O2 substituents would be directed closer to the protein surface and provide opportunity to design inhibitors that are more specific toward particular galectins. Our elucidation of X-ray crystal structures of two of our synthesised talosides in complex with galectin-1 and galectin-3 provide the first atomic information on the interactions of galectins, and indeed any protein, with talosides. These results have enabled a structure-based rationale for the specificity differences shown by galectin-1 and galectin-3 toward these talosides and demonstrate new opportunities for further exploitation as specific inhibitors of galectins. (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
Chemical Biology and Drug Design
volume
79
issue
3
pages
339 - 346
publisher
Wiley-Blackwell
external identifiers
  • wos:000299253200012
  • pmid:22136701
  • scopus:84856030573
ISSN
1747-0285
DOI
10.1111/j.1747-0285.2011.01283.x
language
English
LU publication?
yes
id
9899d8d7-784d-41db-8ba7-2897fe32bdd8 (old id 2274629)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22136701?dopt=Abstract
date added to LUP
2012-01-03 11:31:22
date last changed
2017-01-08 05:24:31
@article{9899d8d7-784d-41db-8ba7-2897fe32bdd8,
  abstract     = {Galectin-1 and galectin-3 have roles in cancer and inflammation. Galectin-1 has recently emerged as a significant protein produced by tumour cells to promote tumour development, angiogenesis and metastasis and consequently represents an important target to inhibit. The design of inhibitors targeting the carbohydrate recognition domain that is known to recognise galactose is an important approach in the fight against cancer. Based on analysis of crystal structures, we pursued the concept that if the galactose were to be replaced with talose (the C2 epimer of galactose) as a scaffold, then O2 substituents would be directed closer to the protein surface and provide opportunity to design inhibitors that are more specific toward particular galectins. Our elucidation of X-ray crystal structures of two of our synthesised talosides in complex with galectin-1 and galectin-3 provide the first atomic information on the interactions of galectins, and indeed any protein, with talosides. These results have enabled a structure-based rationale for the specificity differences shown by galectin-1 and galectin-3 toward these talosides and demonstrate new opportunities for further exploitation as specific inhibitors of galectins.},
  author       = {Collins, Patrick M and Oberg, Christopher T and Leffler, Hakon and Nilsson, Ulf J and Blanchard, Helen},
  issn         = {1747-0285},
  language     = {eng},
  number       = {3},
  pages        = {339--346},
  publisher    = {Wiley-Blackwell},
  series       = {Chemical Biology and Drug Design},
  title        = {Taloside inhibitors of Galectin-1 and Galectin-3.},
  url          = {http://dx.doi.org/10.1111/j.1747-0285.2011.01283.x},
  volume       = {79},
  year         = {2012},
}