Thioureido N-acetyllactosamine derivatives as potent galectin-7 and 9N inhibitors

Summary, in English

Derivatives of N-acetyllactosamine carrying structurally diverse thioureido groups at galactose C3 were prepared from a C3'-azido N-acetyllactosamine derivative in a three-step reaction sequence involving azide reduction and isothiocyanate formation by thiophosgene treatment of the C3-amine, followed by reaction of the isothiocyanate with a panel of amines. Evaluation of the N-acetyllactosamine thioureas as inhibitors against galectins-1, 3, 7, 8N (N-terminal domain), and 9N (N-terminal domain) revealed thiourea-mediated affinity enhancements for galectins-1, 3, 7, and 9N. In particular, good inhibitors were discovered against galectin-7 and 9N (K-d 23 and 47 mu M, respectively, for a 3-pyridylinethylthiourea derivative), which represents more than an order of magnitude affinity enhancement over the parent natural N-acetyllactosamine. (c) 2005 Elsevier Ltd. All rights reserved.

• Författare: Bader Salameh; Anders Sundin; Hakon Leffler; Ulf Nilsson
• Avdelning/ar: Centrum för analys och syntes; Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG
• Publiceringsår: 2006
• Språk: Engelska
• Sidor: 1215-1220
• Publikation/Tidskrift/Serie: Bioorganic & Medicinal Chemistry
• Volym: 14
• Issue: 4
• Länkar: http://dx.doi.org/10.1016/j.bmc.2005.09.050
• Dokumenttyp: Artikel i tidskrift
• Förlag: Elsevier
• Ämne: Microbiology in the medical area; Immunology in the medical area
• Nyckelord: N-acetyllactosamine; thiourea; galectin; inhibitor
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 0968-0896