MODIFICATION OF THE SIALIC-ACID RESIDUES OF CHORIOGONADOTROPIN AFFECTS SIGNAL-TRANSDUCTION

Human choriogonadotropin (hCG) is a glycoprotein hormone that activate s adenylyl cyclase. The carbohydrate moieties of hCG ate required for biological activity, but not for binding to the gonadotropin receptors . We modified N-acetylneuraminic acid (NeuAc) on the oligosaccharide m oieties of hCG, and determined the effect on its biological activity b y measuring hormone-stimulated adenylyl cyclase. Treating hCG with sod ium periodate to remove two carbon atoms from NeuAc or quantitatively removing NeuAc from hCG reduced its biological activity by 36% and 50% , respectively. The galactose residues of asialo-hCG were reacted with NeuAc-hydrazone or a hydrazone of the oligosaccharide from the gangli oside G(M1) (Gal(beta 1-3)GalNAc(beta 1-4)[NeuAc(alpha 2-3)]Gal(beta 1 -4)Glc). The gonadotropin receptor had high affinity for both derivati ves, but their biological activity was less than that of hCG. These re sults suggest that several structural aspects of NeuAc including carbo n side chain, an intact ring structure, and the position of NeuAc rela tive to other carbohydrate residues are important for full biological activity of hCG.