Low micromolar inhibitors of galectin-3 based on 3'-derivatization of N-acetyllactosamine.
(2002) In ChemBioChem 3(2-3). p.183-189- Abstract
- A strategy for generating potential galectin inhibitors was devised based on derivatization at the C-3′ atom in 3′-amino-N-acetyllactosamine by using structural knowledge of the galectin carbohydrate recognition site. A collection of 12 compounds was prepared by N-acylations or N-sulfonylations. Hydrophobic tagging of the O-3 atom in the N-acetylglucosamine residue with a stearic ester allowed rapid and simple product purification. The compounds were screened in a galectin-3 binding assay and three compounds with significantly higher inhibitory activities compared to the parent N-acetyllactosaminide were found. These three best inhibitors all carried an aromatic amide at the C-3′ position of the galactose moiety, which indicates that... (More)
- A strategy for generating potential galectin inhibitors was devised based on derivatization at the C-3′ atom in 3′-amino-N-acetyllactosamine by using structural knowledge of the galectin carbohydrate recognition site. A collection of 12 compounds was prepared by N-acylations or N-sulfonylations. Hydrophobic tagging of the O-3 atom in the N-acetylglucosamine residue with a stearic ester allowed rapid and simple product purification. The compounds were screened in a galectin-3 binding assay and three compounds with significantly higher inhibitory activities compared to the parent N-acetyllactosaminide were found. These three best inhibitors all carried an aromatic amide at the C-3′ position of the galactose moiety, which indicates that favorable interactions were formed between the aromatic group and galectin-3. The best inhibitor had an IC50 value (4.4 μM) about 50 times better than the parent N-acetyllactosaminide, which implies that it has potential as a valuable tool for studying galectin-3 biological functions and also as a lead compound for the development of galectin-3-blocking pharmaceuticals. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/107233
- author
- Sörme, Pernilla LU ; Qian, Yuning LU ; Nyholm, Per-Georg ; Leffler, Hakon LU and Nilsson, Ulf J. LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Amino Sugars : pharmacology, Enzyme-Linked Immunosorbent Assay, Drug Design, Binding Sites, Antigens, Differentiation : immunology, Amino Sugars : chemical synthesis
- in
- ChemBioChem
- volume
- 3
- issue
- 2-3
- pages
- 7 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000174383700007
- scopus:0036523463
- pmid:11921396
- ISSN
- 1439-4227
- DOI
- 10.1002/1439-7633(20020301)3:2/3<183::aid-cbic183>3.0.co;2-%23
- language
- English
- LU publication?
- yes
- id
- 16a582fb-8cb8-4f84-bd7c-7bac581d5025 (old id 107233)
- alternative location
- http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11921396&dopt=Abstract
- date added to LUP
- 2016-04-01 11:48:15
- date last changed
- 2023-02-22 12:21:19
@article{16a582fb-8cb8-4f84-bd7c-7bac581d5025,
abstract = {{A strategy for generating potential galectin inhibitors was devised based on derivatization at the C-3′ atom in 3′-amino-N-acetyllactosamine by using structural knowledge of the galectin carbohydrate recognition site. A collection of 12 compounds was prepared by N-acylations or N-sulfonylations. Hydrophobic tagging of the O-3 atom in the N-acetylglucosamine residue with a stearic ester allowed rapid and simple product purification. The compounds were screened in a galectin-3 binding assay and three compounds with significantly higher inhibitory activities compared to the parent N-acetyllactosaminide were found. These three best inhibitors all carried an aromatic amide at the C-3′ position of the galactose moiety, which indicates that favorable interactions were formed between the aromatic group and galectin-3. The best inhibitor had an IC50 value (4.4 μM) about 50 times better than the parent N-acetyllactosaminide, which implies that it has potential as a valuable tool for studying galectin-3 biological functions and also as a lead compound for the development of galectin-3-blocking pharmaceuticals.}},
author = {{Sörme, Pernilla and Qian, Yuning and Nyholm, Per-Georg and Leffler, Hakon and Nilsson, Ulf J.}},
issn = {{1439-4227}},
keywords = {{Amino Sugars : pharmacology; Enzyme-Linked Immunosorbent Assay; Drug Design; Binding Sites; Antigens; Differentiation : immunology; Amino Sugars : chemical synthesis}},
language = {{eng}},
number = {{2-3}},
pages = {{183--189}},
publisher = {{John Wiley & Sons Inc.}},
series = {{ChemBioChem}},
title = {{Low micromolar inhibitors of galectin-3 based on 3'-derivatization of <i>N</i>-acetyllactosamine.}},
url = {{http://dx.doi.org/10.1002/1439-7633(20020301)3:2/3<183::aid-cbic183>3.0.co;2-%23}},
doi = {{10.1002/1439-7633(20020301)3:2/3<183::aid-cbic183>3.0.co;2-%23}},
volume = {{3}},
year = {{2002}},
}