African warriors and hunters traditionally used Ouabainas a heart-stopping poison on their arrows. Two types of African plants make ouabain. Mammals also produce it in their bodies, though at lower levels that are thought to help control blood pressure; doctors sometimes prescribe small doses of the compound to treat heart attack patients.
‘A subunit of the plant extract ouabain called α4 which is found only in sperm cells can be critical in male fertility.’
Ouabain disrupts the passage of sodium and calcium ions through the membrane protein Na, K-ATPases, which are found in cell membranes and are made up of protein subunits.
Some subunits are found in cardiac tissue, but one type of subunit called α4 is found only in sperm cells. This protein is known to be critical in fertility -- at least in male mice.
Ouabain binds strongly to α4, but it also binds to other Na,K-ATPase subunits, albeit less tightly. Prior clinical studies have shown that ouabain curbs fertility in men. However, ouabain itself isn't an option as a contraceptive because of the risk of heart damage.
So Gunda Georg, Gustavo Blanco, and colleagues set out to design ouabain analogs that are far more likely to bind to the α4 protein in sperm than to subunits found in heart tissue.