Lactotriaose-containing carbosilane dendrimers: Syntheses and lectin-binding activities

Carbosilane dendrimers periphery-functionalized with lactotriaose (GlcNAc beta 1-3Gal beta l-4Glc) with valencies of three, four, six, and twelve were prepared for use in a lectin-binding assay. A lactotriaose derivative was prepared from D-glucosamine and D-lactose derivatives. The N-Troc-protected glucosamine glycosyl donor and 3'-O-unprotected lactose glycosyl acceptor were condensed in the presence of silver trifluoromethanesulfonate and methylsulfenyl bromide to provide corresponding trisaccharide with new beta-1-3 linkages in 92% yield. The protection group of the trisaccharide was transformed into an acetyl group. The 4-pentenyl glycoside was prepared from the acetate via glycosyl bromide. The alkene was converted into acetyl sulfide by addition of thioacetic acid under radical conditions. The lactotriaose unit was linked with carbosilane dendrimers to afford acelyl-protected glycodendrimers. De-O-acetylation of the dendrimers was carried out in the presence of sodium methoxide and then aq NaOH to give the desired lactotriaose clusters using a carbosilane dendrimer backbone. Their biological activities toward WGA were evaluated by fluorescence methods. The binding constants of free lactotriaose and trivalent, tetravalent, hexavalent, and dodecavalent glycodendrimers to WGA were determined to be 1.1 x 10(3), 4.4 x 10(4), 5.1 x 10(4), 2.8 x 10(6), and 1.3 x 10(6) M-1, respectively. The hexavalent glycodendrimer showed a 2500-fold larger binding effect than that of free lactotriaose. (c) 2006 Elsevier Ltd. All rights reserved.