원문정보
초록
영어
Polo-like kinase 1 (Plk1) plays crucial roles in various stages of oocyte maturation. Recently, we demonstrated that synthesized peptidomimetics AB103-8, targeting the polo- box domain (PBD) of Plk1 disrupted oocyte meiotic maturation and meiosis resumption. However, as a peptidic character of AB103-8 appeared to be defective due to poor membrane permeability and protease stability. To overcome the drawbacks, we designed and synthesized a series of pyrrole-based small-molecule inhibitors and screened against porcine oocyte maturation rates. Among the synthesized compounds, the macrocyclic inhibitor compound 4 displayed the highest inhibition potential against the oocyte meiotic maturation and embryos blastocyst formation. Furthermore, the addition of this compound to culture medium efficiently blocked the maturation of porcine and mouse oocytes, indicating that the lead compound could penetrate zona pellucida and cell membrane. We also investigated the Plk1 inhibiting ability of this compound. Treated mouse oocytes confirmed the Plk1 inhibition by showing abnormal spindle formation. Collectively, these results suggest that the novel Pyrrole-based compounds could be used for the basis of developing contraceptive agents.