کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1365965 | 981577 | 2006 | 6 صفحه PDF | دانلود رایگان |
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 (Kd 23 and 47 μM, respectively, for a 3-pyridylmethylthiourea derivative), which represents more than an order of magnitude affinity enhancement over the parent natural N-acetyllactosamine.
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Journal: Bioorganic & Medicinal Chemistry - Volume 14, Issue 4, 15 February 2006, Pages 1215–1220