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Structure-based design and protein engineering of intersubunit disulfide bonds in gonadotropins

Nature Biotechnology volume 15, pages 658–662 (1997)Cite this article

Abstract

Pairs of cystine residues were introduced in the α- and β-subunits of human choriogonadotropin at positions with optimal geometries for the formation of disulfide bonds. Using the homology with luteiniz-ing hormone and follicle stimulating hormone, similar mutations were carried out in these glycoprotein hormones. In nearly all mutants the corresponding disulfide bonds were formed leading to a non-natural, covalent linkage between the α- and β-subunits. The mutants typically display wild-type receptor binding and bioactivity. The mutants with non-natural intersubunit disulfide bonds display enhanced thermostabilities relative to the corresponding heterodimeric glycoprotein hormones, rendering them candidates for long acting gonadotropins with enhanced shelf lives.

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Authors and Affiliations

  1. N.V Organon, P.O. Box 20, 5340 BH Oss, The Netherlands

    Judith C. Heikoop, Paul van den Boogaart, John WM Mulders & Peter D.J. Grootenhuis

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  1. Judith C. Heikoop
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  2. Paul van den Boogaart
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  3. John WM Mulders
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  4. Peter D.J. Grootenhuis
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Heikoop, J., Boogaart, P., Mulders, J. et al. Structure-based design and protein engineering of intersubunit disulfide bonds in gonadotropins. Nat Biotechnol 15, 658–662 (1997). https://doi.org/10.1038/nbt0797-658

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