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Primary Evaluation of Potential Small Molecule Inhibitors of the Astacin Metalloproteinase Ovastacin, A Novel Drug Target in Female Infertility Treatment

preprint
submitted on 02.12.2019 and posted on 11.12.2019 by Hagen Körschgen, Christian Jäger, Kathrin Tan, Mirko Buchholz, Walter Stöcker, Daniel Ramsbeck

Despite huge progress in hormonal therapy and improved in vitro fertilization methods, the success rates in infertility treatment are still limited. A recently discovered mechanism revealed the interplay between the plasma protein fetuin-B and the cortical granule-based proteinase ovastacin as novel key-mechanism in the regulation of fertilization. Upon sperm-egg fusion, cleavage of a distinct zona pellucida component by ovastacin destroys the sperm receptor, enhances zona robustness and eventually provides a definitive block against polyspermy. An untimely onset of this zona hardening prior to fertilization would consequently result in infertility. Physiologically, this process is controlled by fetuin-B, an endogenous ovastacin inhibitor. Here we aimed at the discovery of small molecular inhibitors of ovastacin that could mimic the effect of fetuin-B. Hence, these compounds could be useful lead structures for the development of specific ovastacin inhibitors that can be utilized in infertility treatment or in vitro fertilization.

History

Email Address of Submitting Author

daniel.ramsbeck@izi.fraunhofer.de

Institution

Fraunhofer Institute for Cell Therapy and Immunology IZI

Country

Germany

ORCID For Submitting Author

0000-0002-4966-142X

Declaration of Conflict of Interest

no conflict of interest

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