INHIBITION OF THE TYPE-1 FIMBRIAE-MEDIATED ADHESION OF ESCHERICHIA-COLI TO ERYTHROCYTES BY MULTIANTENNARY ALPHA-MANNOSYL CLUSTERS - THE EFFECT OF MULTIVALENCY

alpha-Mannosyl glycoclusters and glycodendrimers were tested as multiv alent inhibitors of the type 1 (mannose-specific) fimbriae of a recomb inant E. coli HB101 strain. Inhibition of haemagglutination of guinea pig erythrocytes was determined on microtiter plates. The effect of mu ltivalency is pronounced for up to three mannosyl residues in the mole cule, whereas larger derivatives do not have an appreciable effect on binding to the fimbrial carbohydrate binding domain. The best glycoclu sters tested reach the binding potency of the known potent inhibitor p NPMan (3). The results support the idea of a monovalent recognition si te at the adhesive protein FimH, which might best accommodate molecule s with the size of a trisaccharide or those which expose up to three a lpha-mannosyl residues, such as the glycocluster 8. The results obtain ed with the thiourea-bridged alpha-mannosyl clusters, possessing defin ed sugar valencies, facilitate the development of high affinity inhibi tors of the fimbrial lectin on type 1 fimbriae.