Taloside Inhibitors of Galectin-1 and Galectin-3
(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 recognize galactose is an important approach in the fight against cancer. Based on the analysis of crystal structures, we pursued the concept that if the galactose was 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 towards 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 recognize galactose is an important approach in the fight against cancer. Based on the analysis of crystal structures, we pursued the concept that if the galactose was 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 towards particular galectins. Our elucidation of X-ray crystal structures of two of our synthesized talosides in complex with galectin-1 and galectin-3 provides 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 towards these talosides and demonstrate new opportunities for further exploitation as specific inhibitors of galectins.
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- author
- Collins, Patrick M. ; Öberg, Christopher T. LU ; Leffler, Hakon LU ; Nilsson, Ulf J. LU and Blanchard, Helen
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Carbohydrates, Galectin, Inhibitor design, Protein X-ray crystal structures, Talosides
- in
- Chemical Biology and Drug Design
- volume
- 79
- issue
- 3
- pages
- 8 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000299253200012
- pmid:22136701
- scopus:84856030573
- pmid:22136701
- 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
- 2016-04-04 08:18:43
- date last changed
- 2023-05-15 08:27:53
@article{9899d8d7-784d-41db-8ba7-2897fe32bdd8,
abstract = {{<p>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 recognize galactose is an important approach in the fight against cancer. Based on the analysis of crystal structures, we pursued the concept that if the galactose was 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 towards particular galectins. Our elucidation of X-ray crystal structures of two of our synthesized talosides in complex with galectin-1 and galectin-3 provides 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 towards these talosides and demonstrate new opportunities for further exploitation as specific inhibitors of galectins.</p>}},
author = {{Collins, Patrick M. and Öberg, Christopher T. and Leffler, Hakon and Nilsson, Ulf J. and Blanchard, Helen}},
issn = {{1747-0285}},
keywords = {{Carbohydrates; Galectin; Inhibitor design; Protein X-ray crystal structures; Talosides}},
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}},
doi = {{10.1111/j.1747-0285.2011.01283.x}},
volume = {{79}},
year = {{2012}},
}