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.
摘要:
不可解离的促性腺激素可以通过天然异二聚体激素的化学交联或通过融合其α和β多肽序列表达重组单链分子来获得。这些不可解离的激素并不比它们的天然异二聚体更活跃,这表明包含α亚基的β亚基安全带确保了αβ异二聚体在生理条件下的稳定性。单链促性腺激素的主要利益是,1/仅需要一个单一的质粒来产生活性重组激素,2/两个亚基结构域恒定地以等量存在,并且3/它们甚至在低浓度下保持紧密接近以形成激素生物活性3D结构。这些不可解离的促性腺激素已显示出优异的稳定性和活性,但它们尚未商业化,可能是因为免疫原性风险和生产成本。然而,它们可能被用作化学上更简单和更便宜的LH和FSH受体配体开发的基础。