Synthesis of Fucopeptides as Sialyl Lewis' Mimetics

摘要

The Ca~(2+)-dependent interaction between E-selectin of endothelial cells and sialyl Lewis~x (SLe~x) of neutrophils is a critical carbohydrate-protein recognition event that occurs shortly after tissue injury and leads to acute and chronic inflammations. E-selectin is also inducibly expressed in response to inflammatory factors such as tumor necrosis factor (TNF), interleukin-lb (IL-lb), leukotriene B_4, neurotoxins. and endotoxins. while SLe~x is presented by glycoproteins and/or glycolipids on theneutrophil surface. Thus, blocking the SLe~x/E-selectin interaction has been considered to be an effective way to treat neuirophil-mediated inflammatory diseases. Although SLe~x has been considered as an antiinflammatory agent, this tetrasaccharide can only be used in acute cases, as it is unstable in the blood and orally inactive. In addition, it is generally difficult to synthesize oligosaccharides on a large scale. It is therefore of great interest to develop oligosaccharide mimetics that are more stable and active, possess better bioavailability, and are easier to make.