Converting heterodimeric gonadotropins to genetically linked single chains: new approaches to structure activity relationships and analogue design.

One of the distinguishing features of the gonadotropin and thyrotropin hormone family is their heterodimeric structure; the subunits combine early in the secretory pathway and only the dimers are capable of binding to receptors. Therefore, assembly is rate limiting in the production of functional heterodimers, a problem encountered when removing the carbohydrates from one or both subunits as discussed in this review. If the heterodimers can be expressed as single chains, this might avoid mutagenesis-induced defects in secretion and combination of individual subunits for structure-function studies and analogue design. Here we discuss the feasibility of this approach for such problems.