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Towards minimized gonadotropins with full bioactivity.

J C Heikoop·B Huisman-de Winkel·P D Grootenhuis
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Abstract

Gonadotropins are highly complex glycoprotein hormones consisting of two noncovalently associated subunits, which are heavily glycosylated. Using the X-ray structure of human choriogonadotropin and structure/activity relationships we aimed to design 'minimized' gonadotropins of reduced complexity. Our results show that it is possible to reduce the size of natural human choriogonadotropin by one-third of its molecular weight while retaining its wild-type biopotency. To our knowledge, such 'mini'-human choriogonadotropins represent the smallest gonadotropins described so far with an lutropin/choriogonadotropin receptor affinity and in vitro biological activity comparable with that of natural human choriogonadotropin. It provides an important step towards the structure/function-based design of small molecule drugs to the human gonadotropin receptors.

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AnimalsCHO CellsChorionic GonadotropinCricetinaeDrug DesignGenes, ReporterHumansIn Vitro TechniquesLuciferasesMolecular WeightMutagenesis, Site-DirectedPeptide FragmentsProtein ConformationReceptors, LHStructure-Activity RelationshipJournal Article

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J C Heikoop, B Huisman-de Winkel, P D Grootenhuis. 1999. Towards minimized gonadotropins with full bioactivity.. https://doi.org/10.1046/j.1432-1327.1999.00232.x

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