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The Fungal Sexual Pheromone Sirenin Activates the Human CatSper Channel Complex

  • Author(s): Syeda, SS
  • Carlson, EJ
  • Miller, MR
  • Francis, R
  • Clapham, DE
  • Lishko, PV
  • Hawkinson, JE
  • Hook, D
  • Georg, GI
  • et al.
Abstract

© 2015 American Chemical Society. The basal fungus Allomyces macrogynus (A. Macrogynus) produces motile male gametes displaying well-studied chemotaxis toward their female counterparts. This chemotaxis is driven by sirenin, a sexual pheromone released by the female gametes. The pheromone evokes a large calcium influx in the motile gametes, which could proceed through the cation channel of sperm (CatSper) complex. Herein, we report the total synthesis of sirenin in 10 steps and 8% overall yield and show that the synthetic pheromone activates the CatSper channel complex, indicated by a concentration-dependent increase in intracellular calcium in human sperm. Sirenin activation of the CatSper channel was confirmed using whole-cell patch clamp electrophysiology with human sperm. Based on this proficient synthetic route and confirmed activation of CatSper, analogues of sirenin can be designed as blockers of the CatSper channel that could provide male contraceptive agents.

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