1. Towards minimized gonadotropins with full bioactivity.
- Author
-
Heikoop JC, Huisman-de Winkel B, and Grootenhuis PD
- Subjects
- Animals, CHO Cells, Chorionic Gonadotropin genetics, Cricetinae, Drug Design, Genes, Reporter, Humans, In Vitro Techniques, Luciferases genetics, Molecular Weight, Mutagenesis, Site-Directed, Peptide Fragments chemistry, Peptide Fragments genetics, Peptide Fragments pharmacology, Protein Conformation, Receptors, LH drug effects, Receptors, LH metabolism, Structure-Activity Relationship, Chorionic Gonadotropin chemistry, Chorionic Gonadotropin pharmacology
- 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.
- Published
- 1999
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