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Discovery of specific activity of 2-HPA acting on the membrane progestin receptor α (paqr7) by purification of natural products from the marine algae Padina

Amin, M. T.; Acharjee, M.; Jyoti, M. M. S.; Rezanujjaman, M.; Hassan, M. M.; Hossain, M. F.; Ahamed, S.; Kodani, S.; Tokumoto, T.

2023-09-12 biochemistry
10.1101/2023.09.12.557470 bioRxiv
Show abstract

Membrane progestin receptors (mPRs) are members of the progestin and adipoQ (PAQR) receptor family that are stimulated by endogenous steroids to initiate rapid intracellular signalling through a nongenomic pathway. Previously, water-soluble compounds with mPR-binding activity from the marine algae Padina arborescens were fractionated by HPLC steps. In this study, the structure of one of the major compounds in the fraction was identified as 2-hydroxypentanoic acid (2-HPA) using Nuclear Magnetic Resonance spectroscopy. 2-HPA showed a substantial competitive binding affinity for hmPR in the GQD-hmPR binding assay. In contrast, synthetic structural analogues of 2-HPA showed no competitive binding activity. The physiological activity of 2-HPA and its analogues was then investigated using in vitro goldfish and in vivo zebrafish oocyte maturation and ovulation assays. As with the hmPR binding assay, only 2-HPA showed inhibitory activity on oocyte maturation and ovulation of fish oocytes. Furthermore, the inhibitory activity of 2-HPA was compared between S- and R-type 2-HPA. The results showed that both types had the same level of activity. These results indicate that 2-HPA, found as a secreted compound from Padina arborescens, is a novel mPR antagonist and its chemical structure is highly restricted to show its activity.

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