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

11 December 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

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.

Keywords

ovastacin
astacins
metalloproteinase
metzincins
fetuin-B
infertility
in vitro
fertilization
hydroxamate

Supplementary materials

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Primary evaluation of potential small molecule inhibitors of the astacin proteinase Ovastacin SI
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