SYNTHESIS OF A SIALYL-LEWIS-X MIMIC WITH FIXED CARBOXYLIC-ACID GROUP - CHEMICAL APPROACH TOWARD THE ELUCIDATION OF THE BIOACTIVE CONFORMATION OF SIALYL-LEWIS-X

The relation of the solution and bioactive conformation of sialyl Lewi s x (sLe(x)) has been addressed by chemical means. To mimic the prefer red solution conformation of sLe(x) 1, the more rigid analog 2 has bee n designed and synthesized. The sialic acid residue of 1 was replaced by a carboxylic acid function which is fixed in the equatorial positio n of a six membered ring acetal fused to galactose. Due to entropic co nsiderations, an increased biological activity could be expected if th e preferred solution conformation and bound form of sLe(x) were simila r. Since mimic 2 was found to be inactive in an E-selectin binding ass ay, the bound form of sLe(x) most probably differs from the prevailing solution conformation.