Undissociable chemically cross-linked and single-chain gonadotropins

Abstract

Undissociable gonadotropins can be obtained either by chemical cross-linking of the natural heterodimeric hormones or by expressing recombinant single-chain molecules through the fusion of their α and β polypeptide sequences. These undissociable hormones are not more active than their natural heterodimeric counterparts indicating that the β-subunit seatbelt embracing the α-subunit ensures the αβ heterodimer stability in physiological conditions. The main interests of single-chain gonadotropins are that 1/only one single plasmid is required to produce an active recombinant hormone, 2/the two subunits' domains are constantly present in equal amounts and 3/they remain in close proximity even at low concentration for forming the hormone bioactive 3D structure. These undissociable gonadotropins have been shown to exhibit excellent stability and activity but they have not yet been commercialized probably because of immunogenicity risks and cost of production. Nevertheless, they might be used as a basis for the development of chemically simpler and cheaper ligands of LH and FSH receptors.