Abstract

Multiple articles have been published describing the N-linked and O-linked oligosaccharide structures of hCG. All, however, have used purified preparation from pregnancy urine and from choriocarcinoma patient urine. This has told the scientific community that pregnancy and choriocarcinoma hCG-related molecules contain Type 1 and Type 2 O-linked oligosaccharides and biantennary and triantennary N-linked oligosaccharide. Recent years have seen the demonstration of two completely independent hCG molecules, hCG and hyperglycosylated hCG. hCG is a pregnancy hormone made by syncytiotrophoblast cell. Hyperglycosylated hCG is a TGFs receptor binding autocrine produced by cytotrophoblast cells. The two independent share a common amino acid sequence and just vary in carbohydrate structure. Unfortunately, all the carbohydrate structure reports are on a mixture of hCG and hyperglycosylated hCG, as present in pregnancy and choriocarcinoma. This does not all anyone to clearly see the carbohydrate structural differences between the two molecules. Here we carefully examine the carbohydrate structural differences between hCG and hyperglycosylated hCG using the B152 hyperglycosylated hCG-specific immunoassay. It is shown that hCG has only Type 1 O-linked oligosaccharides, while hyperglycosylated hCG only has Type 2 O-linked oligosaccharides. Type of O-linked oligosaccharide structure completely distinguishes hCG and hyperglycosylated hCG.

Highlights

  • The O-linked and N-linked oligosaccharide structures of human chorionic gonadotropin has been studied very thoroughly by multiple groups [1,2,3,4,5,6]

  • All oligosaccharide structures found on human chorionic gonadotropin (hCG) and hyperglycosylated hCG by these investigators are shown in Figure 1 (NM, NNF and NNF biantennary N-linked structures, NNM, NNN, NNNF triantennary N-linked structures, Bi, Tetra1, Tri1 and Tri2 Type 1 O-linked oligosaccharides, and Tetra2, Hexa, Penta1 and Penta 2 Type 2 O-linked oligosaccharides)

  • We examine for the first time the real structures of oligosaccharides attached to the autocrine hyperglycosylated hCG and the hormone hCG

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Summary

Introduction

The O-linked and N-linked oligosaccharide structures of human chorionic gonadotropin (hCG) has been studied very thoroughly by multiple groups [1,2,3,4,5,6]. It has been studied by glycosidase digestion methods [1,2,3], by gel filtration oligosaccharide separation [4], by Dionex oligosaccharide-specific HPLC [5], and by mass spectrometry methods [6]. All reports show structure of a invariable mixture of the hormone hCG and a completely independent molecule, the autocrine hyperglycosylated hCG. It is only in recent years, after most of these carbohydrate structure projects were completed [1,2,3,4,5], that the presence of two separate molecules in pregnancy, a hormone and an autocrine, has been demonstrated [7,8,9]

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