In silico Docking Analysis for Blocking JUNO-IZUMO1 Interaction Identifies Two Small Molecules that Block in vitro Fertilization.
In silico Docking Analysis for Blocking JUNO-IZUMO1 Interaction Identifies Two Small Molecules that Block in vitro Fertilization.
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DOI：
10.3389/fcell.2022.824629
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
联合激素药物是口服避孕药的基础。然而，它们与严重的副作用有关，这些副作用对资源有限的发展中国家的妇女影响更大。副作用的风险可以通过非激素小分子来降低，这些小分子专门针对参与受精的蛋白质。在这项研究中，我们提出了一个虚拟的对接实验，旨在发现针对JUNO（卵母细胞）和IZUMO 1（精子）的关键受精相互作用的分子。我们将913，000个分子与JUNO的两种晶体结构对接，并根据能量相关标准对它们进行排名。在32个测试的候选者中，两个分子（即，Z786028994和Z1290281203）在小鼠体外受精（IVF）试验和人精子体外穿透仓鼠卵母细胞试验中均表现出受精抑制作用。尽管对受精有明显的影响，但这两种分子并没有显示出JUNO-IZUMO 1相互作用的阻断活性，这是通过基于亲和力的细胞外相互作用筛选（AVEXIS）评估的。因此，需要进一步的研究来确定这两种受精抑制剂的作用机制。
Combined hormone drugs are the basis for orally administered contraception. However, they are associated with severe side effects that are even more impactful for women in developing countries, where resources are limited. The risk of side effects may be reduced by non-hormonal small molecules which specifically target proteins involved in fertilization. In this study, we present a virtual docking experiment directed to discover molecules that target the crucial fertilization interactions of JUNO (oocyte) and IZUMO1 (sperm). We docked 913,000 molecules to two crystal structures of JUNO and ranked them on the basis of energy-related criteria. Of the 32 tested candidates, two molecules (i.e., Z786028994 and Z1290281203) demonstrated fertilization inhibitory effect in both an in vitro fertilization (IVF) assay in mice and an in vitro penetration of human sperm into hamster oocytes. Despite this clear effect on fertilization, these two molecules did not show JUNO–IZUMO1 interaction blocking activity as assessed by AVidity-based EXtracellular Interaction Screening (AVEXIS). Therefore, further research is required to determine the mechanism of action of these two fertilization inhibitors.
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影响因子：
2.9
作者：
Sabatini, Rosa;Cagiano, Raffaele
通讯作者：
Cagiano, Raffaele
影响因子：
3.7
作者：
Beard H;Cholleti A;Pearlman D;Sherman W;Loving KA
通讯作者：
Loving KA
影响因子：
64.8
作者：
Aydin H;Sultana A;Li S;Thavalingam A;Lee JE
通讯作者：
Lee JE
DOI：
10.3791/3881
发表时间：
2012-03-05
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Kerr JS;Wright GJ
通讯作者：
Wright GJ
影响因子：
2.9
作者：
O'Connell, Katharine;Davis, Anne R.;Kerns, Jermifer
通讯作者：
Kerns, Jermifer