Palcic M M, Li H, Zanini D, Bhella R S, Roy R
Department of Chemistry, University of Alberta, Edmonton, Canada.
Carbohydr Res. 1997 Dec;305(3-4):433-42. doi: 10.1016/s0008-6215(97)00263-2.
Traditional structure activity relationship studies (SAR) have led to the development of numerous sialyl Lewis(x) analogs in the search for potential antiinflammatory agents. However, these methods do not take into account cluster or multivalent effects. Reported herein is the chemoenzymatic synthesis of di-, tetra-, and octa-valent sLe(x) ligands scaffolded on dendrimers. Hypervalent L-lysine cores with covalently attached 2-acetamido-2-deoxy-D-glucose (N-acetylglucosamine, GlcNAc) residues were chemically prepared and enzymatically transformed into sLe(x) containing dendrimers so that multivalency, and its role in selectin-sLe(x) interactions may be evaluated. This work constitutes another successful enzymatic synthesis of sLe(x) and represents the first example of GlcNAc elongation on a synthetic dendrimer scaffold. These sLe(x) dendrimers are currently being investigated as selectin antagonists.
传统的构效关系研究（SAR）促使人们在寻找潜在抗炎剂的过程中开发了众多唾液酸化路易斯（x）类似物。然而，这些方法并未考虑簇集或多价效应。本文报道了以树枝状大分子为支架的二价、四价和八价唾液酸化路易斯（x）配体的化学酶法合成。通过化学方法制备了具有共价连接的2-乙酰氨基-2-脱氧-D-葡萄糖（N-乙酰葡糖胺，GlcNAc）残基的高价L-赖氨酸核心，并通过酶法将其转化为含唾液酸化路易斯（x）的树枝状大分子，以便评估多价性及其在选择素-唾液酸化路易斯（x）相互作用中的作用。这项工作是唾液酸化路易斯（x）的又一次成功的酶法合成，也是在合成树枝状大分子支架上进行GlcNAc延伸的首个实例。目前正在研究这些唾液酸化路易斯（x）树枝状大分子作为选择素拮抗剂的性能。
