STRUCTURAL-ANALYSIS OF THE OLIGOSACCHARIDES DERIVED FROM GLYCODELIN, A HUMAN GLYCOPROTEIN WITH POTENT IMMUNOSUPPRESSIVE AND CONTRACEPTIVE ACTIVITIES

Glycodelin, also known as placental protein 14 (PP14) or progesterone- associated endometrial protein (PAEP), is a human glycoprotein with po tent immunosuppressive and contraceptive activities. In this paper we report the first characterization of glycodelin-derived oligosaccharid es. Using strategies based upon fast atom bombardment and electrospray mass spectrometry we have established that glycodelin is glycosylated at Asn-28 and Asn-63. The Asn-28 site carries high mannose, hybrid an d complex-type structures, whereas the second site is exclusively occu pied by complex-type glycans. The major non-reducing epitopes in the c omplex-type glycans are: Gal beta 1-4GlcNAc (lacNAc), GalNAc beta 1-4G lcNAc (lacdiNAc), NeuAc alpha 2-GGal beta 1-4GlcNAc (sialylated lacNAc ), NeuAc alpha 2-6GalNAc beta 1-4GlcNAc (sialylated lacdiNAc), Gal bet a 1-4(Fuc alpha 1-3)GlcNAc (Lewis(x)), and GalNAc beta 1-4(Fuc alpha 1 -3)GlcNAc (lacdiNAc analogue of Lewis(x)). It is possible that the oli gosaccharides bearing sialylated lacNAc or lacdiNAc antennae may manif est immunosuppressive effects by specifically blocking adhesive and ac tivation-related events mediated by CD22, the human B cell associated receptor. Oligosaccharides with fucosylated lacdiNAc antennae have pre viously been shown to potently block selectin-mediated adhesions and m ay perform the same function in glycodelin, The potent inhibitory effe ct of glycodelin on initial human sperm-zona pellucida binding is cons istent with our previous suggestion that this cell adhesion event requ ires a selectin-like adhesion process. This result also raises the pos sibility that a convergence between immune and gamete recognition proc esses may have occurred in the types of carbohydrate ligands recognize d in the human.