Snake venom could help combat heart disease
Research led by Bath University has uncovered new routes for developing drugs for high blood pressure and heart disease.
The research was led by Professor Acharya in collaboration with the Universities of Leeds and Cape Town.
The scientists created images of the 3D molecular structures of two peptides, including one from snake venom, that inhibit angiotensin-I converting enzyme (ACE)- a key protein that regulates blood pressure.
ACE inhibitors, such as the drug Captopril, are taken by millions of people in the UK to treat high blood pressure and heart disease. However the drugs cause side effects such as a persistent cough and swelling of the face and throat.
It is the first time scientists have been able to see how the peptide binds to ACE at a molecular level
In this Medical Research Council funded study, the team produced images of a snake venom peptide BPPb binding to ACE.
Although this peptide has been identified previously as a possible template for drug design, it is the first time scientists have been able to see at the molecular level how the peptide binds to ACE and blocks its action.
Acharya said: “We found that the BPPb peptide binds to a major portion of the active site of the ACE molecule pushing out a zinc atom which is essential for its correct functioning.
“This is the first time we’ve observed zinc-independent inhibition of ACE, and so these findings highlight a very exciting opportunity to design new antihypertensive drugs based on this peptide.”
In addition, the researchers looked at the structure of angiotensin-II (Ang-II) bound to ACE. Ang-II is a hormone produced by ACE that also inhibits it, creating a feedback loop that stops levels of Ang-II getting too high.
Acharya added: “We already knew that Ang-II blocks ACE, but not how it does this at the molecular level. This study has shown for the first time how ACE self-regulates by producing a molecule that obstructs its active site when the concentration reaches a certain level.”
The next step is to use this structural knowledge as a basis for accelerating the on-going work carried out by Professor Acharya and his collaborators on the development of next generation ACE inhibitors that have improved efficacy and fewer side effects.