Low micromolar inhibitors of galectin-3 based on 3'-derivatization of N-acetyllactosamine.
Författare
Summary, in English
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.
Avdelning/ar
Publiceringsår
2002
Språk
Engelska
Sidor
183-189
Publikation/Tidskrift/Serie
ChemBioChem
Volym
3
Issue
2-3
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
John Wiley & Sons Inc.
Ämne
- Immunology in the medical area
- Microbiology in the medical area
Nyckelord
- Amino Sugars : pharmacology
- Enzyme-Linked Immunosorbent Assay
- Drug Design
- Binding Sites
- Antigens
- Differentiation : immunology
- Amino Sugars : chemical synthesis
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1439-4227