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Low micromolar inhibitors of galectin-3 based on 3'-derivatization of N-acetyllactosamine.

Sörme, Pernilla LU ; Qian, Yuning LU ; Nyholm, Per-Georg; Leffler, Hakon LU and Nilsson, Ulf LU (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)
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author
organization
publishing date
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
2017-08-27 03:54:04
@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},
}