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 microM) 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:
http://lup.lub.lu.se/record/107233
- author
- Sörme, Pernilla LU ; Qian, Yuning LU ; Nyholm, Per-Georg; Leffler, Hakon LU and Nilsson, Ulf 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
- 183 - 189
- publisher
- John Wiley & Sons
- external identifiers
-
- wos:000174383700007
- scopus:0036523463
- ISSN
- 1439-4227
- DOI
- 10.1002/1439-7633(20020301)3:2/3<183::AID-CBIC183>3.0.CO;2-#
- 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
- 2007-07-04 11:45:01
- date last changed
- 2019-01-06 05:55:12
@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 microM) 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},
issn = {1439-4227},
keyword = {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},
series = {ChemBioChem},
title = {Low micromolar inhibitors of galectin-3 based on 3'-derivatization of N-acetyllactosamine.},
url = {http://dx.doi.org/10.1002/1439-7633(20020301)3:2/3<183::AID-CBIC183>3.0.CO;2-#},
volume = {3},
year = {2002},
}