Epimers Switch Galectin-9 Domain Selectivity : 3 N-Aryl Galactosides Bind the C-Terminal and Gulosides Bind the N-Terminal
(2020) In ACS Medicinal Chemistry Letters 11(1). p.34-39- Abstract
A series of 3-deoxy-3-N-arylated-β-d-galactoside and -guloside derivatives have been synthesized by cesium fluoride/trimetylsilylaryl triflate-mediated benzyne generation and N-arylation of 3-deoxy-3-amino-β-d-galactosides and -gulosides, respectively. Evaluation as ligands to galectin-1, 2, 3, 4N (N-terminal domain), 4C (C-terminal domain), 7, 8N, 8C, 9C, and 9N revealed that the galactosides selectively bound galectin-9C, whereas the gulosides selectively bound galectin-9N. Hence, the N-aryl group induces galectin-9 selectivity and the ligand 3C-configuration acts as an epimeric selectivity switch between the two domains of galectin-9. Furthermore, MD simulations revealed that galacto derivatives in galectin-9C and gulo derivatives in... (More)
A series of 3-deoxy-3-N-arylated-β-d-galactoside and -guloside derivatives have been synthesized by cesium fluoride/trimetylsilylaryl triflate-mediated benzyne generation and N-arylation of 3-deoxy-3-amino-β-d-galactosides and -gulosides, respectively. Evaluation as ligands to galectin-1, 2, 3, 4N (N-terminal domain), 4C (C-terminal domain), 7, 8N, 8C, 9C, and 9N revealed that the galactosides selectively bound galectin-9C, whereas the gulosides selectively bound galectin-9N. Hence, the N-aryl group induces galectin-9 selectivity and the ligand 3C-configuration acts as an epimeric selectivity switch between the two domains of galectin-9. Furthermore, MD simulations revealed that galacto derivatives in galectin-9C and gulo derivatives in galectin-9N find stable poses with specific interactions, which proposes a possible explanation to the gal/gulo 9C/9N selectivity.
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- author
- Mahanti, Mukul LU ; Pal, Kumar Bhaskar ; Sundin, Anders P. LU ; Leffler, Hakon LU and Nilsson, Ulf J. LU
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- epimers, Galactose, galectin-9, gulose, N-phenyl, selectivity
- in
- ACS Medicinal Chemistry Letters
- volume
- 11
- issue
- 1
- pages
- 34 - 39
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:31938460
- scopus:85076853871
- ISSN
- 1948-5875
- DOI
- 10.1021/acsmedchemlett.9b00396
- language
- English
- LU publication?
- yes
- id
- f00fefdd-3441-405d-a521-8f6044b727d3
- date added to LUP
- 2020-01-14 12:29:15
- date last changed
- 2024-06-26 09:05:18
@article{f00fefdd-3441-405d-a521-8f6044b727d3, abstract = {{<p>A series of 3-deoxy-3-N-arylated-β-d-galactoside and -guloside derivatives have been synthesized by cesium fluoride/trimetylsilylaryl triflate-mediated benzyne generation and N-arylation of 3-deoxy-3-amino-β-d-galactosides and -gulosides, respectively. Evaluation as ligands to galectin-1, 2, 3, 4N (N-terminal domain), 4C (C-terminal domain), 7, 8N, 8C, 9C, and 9N revealed that the galactosides selectively bound galectin-9C, whereas the gulosides selectively bound galectin-9N. Hence, the N-aryl group induces galectin-9 selectivity and the ligand 3C-configuration acts as an epimeric selectivity switch between the two domains of galectin-9. Furthermore, MD simulations revealed that galacto derivatives in galectin-9C and gulo derivatives in galectin-9N find stable poses with specific interactions, which proposes a possible explanation to the gal/gulo 9C/9N selectivity.</p>}}, author = {{Mahanti, Mukul and Pal, Kumar Bhaskar and Sundin, Anders P. and Leffler, Hakon and Nilsson, Ulf J.}}, issn = {{1948-5875}}, keywords = {{epimers; Galactose; galectin-9; gulose; N-phenyl; selectivity}}, language = {{eng}}, number = {{1}}, pages = {{34--39}}, publisher = {{The American Chemical Society (ACS)}}, series = {{ACS Medicinal Chemistry Letters}}, title = {{Epimers Switch Galectin-9 Domain Selectivity : 3 N-Aryl Galactosides Bind the C-Terminal and Gulosides Bind the N-Terminal}}, url = {{http://dx.doi.org/10.1021/acsmedchemlett.9b00396}}, doi = {{10.1021/acsmedchemlett.9b00396}}, volume = {{11}}, year = {{2020}}, }