Towards minimized gonadotropins with full bioactivity.
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.
Heikoop
J C
JC
Scientific Development Group, N.V. Organon, BH Oss, The Netherlands.
Huisman-de Winkel
B
B
Grootenhuis
P D
PD
D000818:Animals; D016466:CHO Cells; D006063:Chorionic Gonadotropin / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D006224:Cricetinae; D015195:Drug Design; D017930:Genes, Reporter; D006801:Humans; D066298:In Vitro Techniques; D008156:Luciferases / Q000235:genetics; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D011487:Protein Conformation; D011974:Receptors, LH / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D006063:Chorionic Gonadotropin; D010446:Peptide Fragments; D011974:Receptors, LH; D008156:Luciferases