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

6533b82bfe1ef96bd128ceac

RESEARCH PRODUCT

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

Hagen Körschgen Christian Jäger Kathrin Tan Mirko Buchholz Walter Stöcker Daniel Ramsbeck

subject

Models Molecular medicine.medical_treatment Hydroxamic Acids 01 natural sciences Biochemistry Mice Human fertilization In vitro fertilization Drug Discovery General Pharmacology Toxicology and Pharmaceutics Amines Zona pellucida metzincins education.field_of_study Molecular Structure Communication Female infertility Sperm receptor Polyspermy Cell biology medicine.anatomical_structure astacins Hydroxamate Molecular Medicine Female metalloproteinase infertility Infertility Female Infertility endocrine system Cortical granule Biology Small Molecule Libraries Structure-Activity Relationship medicine Animals education Pharmacology In vitro fertilisation Dose-Response Relationship Drug urogenital system 010405 organic chemistry Organic Chemistry in vitro fertilization medicine.disease ovastacin Communications 0104 chemical sciences 010404 medicinal & biomolecular chemistry Biocatalysis Metalloproteases

description

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 to be a 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 to discover small‐molecule inhibitors of ovastacin that could mimic the effect of fetuin‐B. These compounds could be useful lead structures for the development of specific ovastacin inhibitors that can be used in infertility treatment or in vitro fertilization

year	journal	country	edition	language
2020-06-08	ChemMedChem

10.1002/cmdc.202000397 https://pubmed.ncbi.nlm.nih.gov/32946206