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Gonadotropin preparations: past, present, and future perspectives

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Presentation on theme: "Gonadotropin preparations: past, present, and future perspectives"— Presentation transcript:

1 Gonadotropin preparations: past, present, and future perspectives
Fertility and Sterility  Volume 90, Issue 5, Pages S13-S20 (November 2008) DOI: /j.fertnstert Copyright © 2008 American Society for Reproductive Medicine Terms and Conditions

2 Figure 1 Human follitropin and human choriogonadotropin consist of two subunits, the alpha subunit (purple) and the beta subunit (red). There are four carbohydrate attachment sites in follicle-stimulating hormone (FSH). As carbohydrate beyond GlcNac2 was not visible in the FSH crystal structure (1FL7), the structures represented were attached to each site by grafting those structures on to Asn and GlcNAc1 molecules at each site. The carbohydrate chain that if removed does not prevent binding but abrogates signal transduction is seen at the 7 o'clock position (αCHO1). At the 4 o'clock and 5 o'clock positions are the two chains (βCHO1, βCHO2) that are resident on the beta subunit and differ in glycosylation as women age (older women have mostly two chains at this site, and younger women have a mixture of two or no chains at this site). Residues critical for receptor binding are rendered with surfaces (receptor-binding sites) as verified in the hFSH/hFSHR crystal structure (PDB files 1XWD). Source: Courtesy James A. Dias, Ph.D. Fertility and Sterility  , S13-S20DOI: ( /j.fertnstert ) Copyright © 2008 American Society for Reproductive Medicine Terms and Conditions

3 Figure 2 Human chorionic gonadotropin (hCG) is similar in structural attributes compared with follitropin. A notable exception is the presence of a long carboxy terminal segment that is O-glycosylated (O-linked CHO). This segment is not visible in the hCG crystal structure (PDB files 1XUN and 1HCN), but it is shown here for illustrative purposes. Of importance is that this extension confers a long half-life to hCG; when grafted onto the hFSH beta subunit, this extension likewise confers a longer circulatory half-life to hFSH. The C-terminal extended hFSH is currently in clinical trials. Source: Courtesy James A. Dias, Ph.D. Fertility and Sterility  , S13-S20DOI: ( /j.fertnstert ) Copyright © 2008 American Society for Reproductive Medicine Terms and Conditions


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