Structural analysis of the oligosaccharides derived from glycodelin, a human glycoprotein with potent immunosuppressive and contraceptive activities

Abstract

Glycodelin, also known as placental protein 14 (PP14) or progesterone- associated endometrial protein (PAEP), is a human glycoprotein with potent immunosuppressive and contraceptive activities. In this paper we report the first characterization of glycodelin-derived oligosaccharides. 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 and complex-type structures, whereas the second site is exclusively occupied by complex-type glycans. The major non-reducing epitopes in the complex-type glycans are: Galβ1-4GlcNAc (lacNAc), GalNAcβ1-4GlcNAc (lacdiNAc), NeuAcα2-6Galβ1- 4GlcNAc (sialylated lacNAc), NeuAcα2-6GalNAcβ1-4GlcNAc (sialylated lacdiNAc), Galβ1-4(Fucα1-3)GlcNAc (Lewis(x)), and GalNAcβ1-4(Fucα1- 3)GlcNAc (lacdiNAc analogue of Lewis(x)). It is possible that the oligosaccharides bearing sialylated lacNAc or lacdiNAc antennae may manifest immunosuppressive effects by specifically blocking adhesive and activation- related events mediated by CD22, the human B cell associated receptor. Oligosaccharides with fucosylated lacdiNAc antennae have previously been shown to potently block selectin-mediated adhesions and may perform the same function in glycodelin. The potent inhibitory effect of glycodelin on initial human sperm-zona pellucida binding is consistent with our previous suggestion that this cell adhesion event requires a selectin-like adhesion process. This result also raises the possibility that a convergence between immune and gamete recognition processes may have occurred in the types of carbohydrate ligands recognized in the human.