Faculty of Biological Sciences

Research Bulletin

Snake venom could be used to design new heart disease drugs

9th October 2012

Research has identified two possible new routes for developing novel drugs for high blood pressure and heart disease.

Snake venom could be used to design new heart disease drugsMolecular structure of ACE (red) with Ang-II peptide bound (yellow)

The research, published in the prestigious Nature journal Scientific Reports, was led by Professor K. Ravi Acharya from the University of Bath, in collaboration with the Universities of Leeds (Professor Elwyn Isaac) and Cape Town (Professor Edward Sturrock), South Africa.

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 (hypertension) and heart disease. However the drugs cause side effects such as a persistent cough and angioedema (swelling of the face and throat).

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.

Professor Ravi 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.

Professor Acharya commented: "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.

The scientists will first use computers to predict the action of different drug designs, then take the best drug candidates and test them in vitro, followed by tests in animal models for hypertension.

Further information


Recent Grants

Neil Ranson, Mark Harris, Ade Whitehouse, Peter Stockley, Sheena Radford, Alan Berry, Wellcome Trust (Mar 2016), £1,000,000

Alan Berry, Wellcome Trust (Oct 2015), £752,365

Steve Sait, NERC (Oct 2015), £386,061

Urwin, Howard Atkinson, BBSRC (Oct 2015), £200,293

Eric Hewitt, Andrew Macdonald, Yorkshire Kidney Research Fund (Oct 2015), £46,621

Ade Whitehouse, Alison Ashcroft, Ian Carr, BBSRC (Sep 2015), £438,975

Dave Westhead, Leukaemia & Lymphoma Research Leukaemia & Lymphoma Research (Sep 2015), £430,567

Shaunna Burke, Andrea Utley, Sarah Astill, Arts Council of England (Sep 2015), £80,594

Samit Chakrabarty, Ronaldo Ichiyama, Intl Foundn for Research in Paraplegia (Aug 2015), £93,000

Anastasia Zhuravleva, BBSRC (Jul 2015), £483,019

Alex O'Neill, MRC (Jul 2015), £249,822

Ade Whitehouse, Richard Foster, Cancer Research UK (Jul 2015), £201,034

Ronaldo Ichiyama, Jim Deuchars, Sue Deuchars, Wings For Life Spinal Cord Research (Jul 2015), £123,895

Martin Stacey and colleagues in FMH, MRC (Jun 2015), £426,475

Adrian Goldman, Sarah Harris, Roman Tuma, BBSRC (Jun 2015), £420,693

Elwyn Isaac, EU (Jun 2015), £238,915

Christine Foyer, BBSRC (Jun 2015), £160,401

Adrian Goldman, EU (Jun 2015), £116,331

David Brockwell, Sheena Radford, Innovate UK (Jun 2015), £113,378

Yoselin Benitez-Alfonso, EPSRC (Jun 2015), £93,672

Michelle Peckham, Peter Knight, Thomas Edwards, BBSRC (May 2015), £404,987

Michelle Peckham, Ed White, Peter Knight, BHF (May 2015), £208,184

Dave Westhead, Sheena Radford, Alex Breeze, BBSRC (May 2015), £51,021

Steve Clapcote, Vitaflo International Ltd (May 2015), £33,703

Les Firbank, Joe Holden, Pippa Chapman, NERC (Apr 2015), £388,726

Samit Chakrabarty, David Steenson, BBSRC (Apr 2015), £120,103

Paul Millner, Gin Jose, Sarah Aickin, DSTL Porton Down (Apr 2015), £63,407

Chris Hassell, David Lewis, The Physiological Society (Apr 2015), £6,900

Andrew Tuplin, Royal Society (Mar 2015), £15,000

Yoselin Benitez-Alfonso, Royal Society (Mar 2015), £14,770

Patricija Van Oosten-Hawle, Royal Society (Mar 2015), £13,960

Stuart Egginton, BHF (Mar 2015), £272,979

Keith Hamer, Department of Energy & Climate Change (Mar 2015), £58,066

Andrew Macdonald, Yorkshire Kidney Research Fund (Mar 2015), £41,171

Les Firbank, DEFRA Dept for Env. Food & Rural Affairs (Feb 2015), £20,000

Ian Hope, Marie-Anne Shaw, BBSRC (Jan 2015), £381,998

Paul Knox, BBSRC (Jan 2015), £5,000

Andrew Peel, BBSRC (Jan 2015), £359,077

Christine Foyer, BBSRC (Jan 2015), £408,334

Dave Westhead and colleagues in Experimental Haematology, Cancer Research UK (Jan 2015), £700,521

Mike McPherson, Christoph Walti, DSTL Porton Down (Jan 2015), £625,125

Sheena Radford, Mark Harris, Peter Stockley, Alan Berry, Alex O'Neill, Thomas Edwards, Adrian Goldman, Anastasia Zhuravleva, Wellcome Trust (Jan 2015), £443,015

Alison Ashcroft, Peter Stockley, Sheena Radford, Nicola Stonehouse, David Brockwell, Darren Tomlinson, BBSRC (Jan 2015), £340,937

Bill Kunin, EU (Jan 2015), £157,490

John Colyer, Leeds Teaching Hospitals Charitable Fund (Jan 2015), £40,000

Chris Hassall, Royal Society (Dec 2014), £14,500

Ryan Seipke, Royal Society (Nov 2014), £13,700

Neil Ranson, BBSRC (Nov 2014), £355,253

Alan Berry, Wellcome Trust (Oct 2014), £749,865

Les Firbank, Joe Holden, BBSRC (Oct 2014), £210,302

Darren Tomlinson and colleagues in Chemistry and Pathology, anatomy and Tumour Biology, Dr Hadwen Trusy (Oct 2014), £194,475

Paul Knox, EU (Oct 2014), £167,229

Martin Stacey and colleagues in Medicine & Health, Pfizer (Oct 2014), £90,453

Darren Tomlinson and colleagues in Experimental Oncology, YCR (Oct 2014), £69,480

Andrew Macdonald, Jamel Mankouri, Kidney Research Fund UK (Oct 2014), £58,878

Mike McPherson and colleagues in Dentistry and Engineering, Wellcome Trust (Oct 2014), £58,437

Dave Westhead and colleagues in Experimental Haemotology, Leukaemia & Lymphoma Research (Sep 2014), £281,424

Recent
News

Bats wake up and smell the coffee

20th August 2015

Intensive agriculture is taking a toll on bats in the Western Ghats of India, one of the world’s most biodiverse regions, but shade-grown coffee, remnant rainforest patches and riverine vegetation strips may help struggling species hang on.


Food production shocks 'will happen more often because of extreme weather'

14th August 2015

Professor Tim Benton (biology), from University of Leeds has conducted research that suggests climate change and a rising demand in food from a high population could cause a frightening situation. 


“Brainy” mice raise hope of better treatments for cognitive disorders

14th August 2015

Researchers have created unusually intelligent mice by altering a single gene and as a result the mice were also less likely to feel anxiety or recall fear. 


Study finds non-genetic cancer mechanism

27th July 2015

Cancer can be caused solely by protein imbalances within cells, a study of ovarian cancer has found.


Physiological Society Oral Communication Prize Winners

17th July 2015

Ewan Fowler and Sabine Lotteau from the Cardiovascular, Sport and Exercise Sciences group (School of Biomedical Sciences) have been awarded the Physiological Society’s Oral Communication Prizes


Age doesn’t dull damselflies' love lives

16th July 2015

Aging damselflies never lose their libidos and are just as likely as younger competitors to mate.


The University of Leeds is investing in 250 new academic fellowships.

1st July 2015

Are you one of the 250 Great Minds we are looking for?


Leeds academics recognised for teaching excellence

11th June 2015

Two University of Leeds academics have received a prestigious teaching award, a National Teaching Fellowship.


The Quest to Engineer the Perfect Potato

8th June 2015

Researchers in the U.K. aim for a new commercial potato that resists many of the worst vulnerabilities of potato crops around the world.


Impact
Stories

Dr Simon Goodman has investigated the disease risks to the native Galapagos fauna.

The Ponnambalam laboratory undertakes research relating to cardiovascular diseases and cancer.

Professor Ingham examinines the biological effects of wear particles from joint replacements.

Professors Urwin and Atkinson have developed three novel technologies for nematode control.

All impact stories