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Investigation into ...
Investigation into the Feasibility of Thioditaloside as a Novel Scaffold for Galectin-3-Specific Inhibitors
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Bum-Erdene, Khuchtumur (author)
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Gagarinov, Ivan A. (author)
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Collins, Patrick M. (author)
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Winger, Moritz (author)
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Pearson, Andrew G. (author)
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Wilson, Jennifer C. (author)
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- Leffler, Hakon (author)
- Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine
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- Nilsson, Ulf (author)
- Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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Grice, I. Darren (author)
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Blanchard, Helen (author)
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(creator_code:org_t)
- 2013-07-17
- 2013
- English.
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In: ChemBioChem. - : Wiley. - 1439-4227. ; 14:11, s. 1331-1342
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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- Galectin-3 is extensively involved in metabolic and disease processes, such as cancer metastasis, thus giving impetus for the design of specific inhibitors targeting this -galactose-binding protein. Thiodigalactoside (TDG) presents a scaffold for construction of galectin inhibitors, and its inhibition of galectin-1 has already demonstrated beneficial effects as an adjuvant with vaccine immunotherapy, thereby improving the survival outcome of tumour-challenged mice. A novel approachreplacing galactose with its C2 epimer, taloseoffers an alternative framework, as extensions at C2 permit exploitation of a galectin-3-specific binding groove, thereby facilitating the design of selective inhibitors. We report the synthesis of thioditaloside (TDT) and crystal structures of the galectin-3 carbohydrate recognition domain in complexes with TDT and TDG. The different abilities of galactose and talose to anchor to the protein correlate with molecular dynamics studies, likely explaining the relative disaccharide binding affinities. The feasibility of a TDT scaffold to enable access to a particular galectin-3 binding groove and the need for modifications to optimise such a scaffold for use in the design of potent and selective inhibitors are assessed.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Keyword
- carbohydrates
- chemical synthesis (thioditaloside)
- inhibitors
- molecular dynamics
- protein structures
Publication and Content Type
- art (subject category)
- ref (subject category)
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Bum-Erdene, Khuc ...
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Gagarinov, Ivan ...
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Collins, Patrick ...
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Winger, Moritz
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Pearson, Andrew ...
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Wilson, Jennifer ...
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show more...
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Leffler, Hakon
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Nilsson, Ulf
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Grice, I. Darren
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Blanchard, Helen
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show less...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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ChemBioChem
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Lund University