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 drugstitle=
Molecular 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

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

Paul Knox, EU (Oct 2014), £167,229

Andrew Peel, BBSRC (Sep 2014), £371,598

Lars Jeuken, BBSRC (Sep 2014), £313,463

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

Stuart Egginton, BHF (Aug 2014), £271,094

Darren Tomlinson, Mike McPherson, Technology Strategy Board (Aug 2014), £98,665

Peter Henderson, Leverhulme Trust (Aug 2014), £15,222

Mike McPherson (and colleagues in the School of Chemistry), EPSRC (Jul 2014), £819,880

Peter Stockley, Neil Ranson, BBSRC (Jul 2014), £455,787

Sheena Radford, Univesity of Michigan (Jul 2014), £138,452

Ryan Seipke, British Society Antimicrobial Chemistry (Jun 2014), £11,960

John Trinick, BHF (Jun 2014), £222,614

Chris West, Leverhulme Trust (Jun 2014), £181,241

Jon Lippiat, Darren Tomlinson, BBSRC (May 2014), £125,174

Christine Foyer, Royal Society (May 2014), £24,000

David Brockwell, Sheena Radford, Medimmune Ltd (Apr 2014), £337,661

Peter Stockley, Wellcome Trust (Apr 2014), £251,019

Mike McPherson, Wellcome Trust (Apr 2014), £146,596

Andrew Macdonald, Kidney Research Fund UK (Apr 2014), £127,237

Elwyn Isaac, DEFRA (Apr 2014), £126,512

Mike McPherson (and colleagues in School of Design), Technology Strategy Board (Apr 2014), £114,350

Paul Millner, Peter Stockley, Darren Tomlinson, YCR (Apr 2014), £95,874

Carrie Ferguson, Karen Birch, Shaunna Burke, Heart Research UK (Apr 2014), £60,140

Tim Benton, Technology Strategy Board (Apr 2014), £24,969

Bill Kunin, Technology Strategy Board (Apr 2014), £21,244

Dave Westhead, MRC (Apr 2014), £18,304

Brendan Davies, BBSRC (Mar 2014), £451,829

Jim Deuchars, MRC (Mar 2014), £300,000

Urwin, Howard Atkinson, British Potato Council (Mar 2014), £69,953

Adam Kupinski, Children with Cancer (Mar 2014), £50,000

Anastasia Zhuravleva, Royal Society (Mar 2014), £14,973

Urwin, Howard Atkinson, Agriculture & Horticulture Develpmnt Brd (Mar 2014), £13,990

Alison Baker, Steve Baldwin, BBSRC (Feb 2014), £403,439

Sarah Zylinski, BBSRC (Feb 2014), £355,869

Dave Lewis, Nigel Hooper, Tony Turner, Hugh Pearson, James Duce, Alzheimer's Society (Feb 2014), £29,871

Ronaldo Ichyama, Samit Chakrabarty, International Spinal Research Trust (Jan 2014), £304,600

Brendan Davies, BBSRC/Bayer Crop Science SA-NV (Jan 2014), £470,053

Adrian Goldman, Steve Baldwin, Stephen Muench, Thomas Edwards, Arwen Pearson , BBSRC (Jan 2014), £467,103

Stefan Kepinski, BBSRC (Jan 2014), £359,269

Elwyn Isaac, EU (Jan 2014), £179,445

Dave Westhead, Leukaemia & Lymphoma Research (Jan 2014), £105,937

Eileen Ingham, Joanne Tipper, Depuy International Ltd (Jan 2014), £48,121

John Barr, Thomas Edwards, MRC (Dec 2013), £469,505

Alex O'Neill, MRC (Dec 2013), £349,017

Tim Benton, NERC (Dec 2013), £31,422

Darren Tomlinson, Yorkshire Cancer Research (Nov 2013), £142,334

Nikita Gamper, MRC (Nov 2013), £336,563

Keith Hamer, Alison Dunn, NERC (Nov 2013), £47,233

Alan Berry, Wellcome Trust (Oct 2013), £749,365

Urwin, Howard Atkinson, BBSRC (Oct 2013), £360,508

Eileen Ingham, Stacey-Paul Wilshaw, NHS R&D (Oct 2013), £356,623

Sheena Radford, BBSRC (Oct 2013), £329,906

Nigel Hooper, Alzheimer's Research (Oct 2013), £327,075

Eileen Ingham, EPSRC (Oct 2013), £276,751

David Beech, BHF (Oct 2013), £109,974

Mark Harris, Medical Research Foundation (Oct 2013), £34,455

James Dachtler, Royal Society (Oct 2013), £15,000

Ade Whitehouse, Teresa Rosenbaum Golden Charitable Trust (Oct 2013), £10,000

Jurgen Denecke, BBSRC (Sep 2013), £382,093

Recent News

Guest lecture from Leeds Biochemistry alumnus, Dr Nicholas Lydon

2nd September 2014

Leeds University alumnus Dr Nicholas Lydon, FRS, will visit the University on Monday 29 September to deliver a guest lecture.

more

Healthy Brains at Leeds: Demystifying Dementia event

29th August 2014

Healthy Brains at Leeds: Demystifying Dementia event

more

‘Tickling’ your ear could be good for your heart

20th August 2014

Stimulating nerves in your ear could improve the health of your heart, researchers have discovered.

more

Triathlon win for Alistair Brownlee

28th July 2014

Congratulations to Leeds alumni Alistair and Jonny Brownlee who won a gold and silver medal respectively in the Triathlon at the Commonwealth Games in Glasgow.

more

HRH meets 'Frank' the cycling skeleton

22nd July 2014

HRH the Countess of Wessex visited researchers from the Institute of Medical and Biological Engineering (iMBE), University of Leeds at the Great Yorkshire Show recently.

more

World-leading biophysicist to head Biological Sciences at Leeds

21st July 2014

World-leading biophysicist to head Biological Sciences at Leeds

more

Researchers find clue to stopping Alzheimer's-like diseases

2nd July 2014

Tiny differences in mice that make them peculiarly resistant to a family of conditions that includes Alzheimer's, Parkinson's and Creutzfeldt-Jakob Disease may provide clues for treatments in humans. more

Impact Stories

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

Professor Sheena Radford has undertook research to determine how peptides self-aggregate and form fibrils under certain conditions.
more

Badrilla is working with outstanding academic collaborators to develop new technologies for calibration of immunoassays.
more

Professor Tim Benton has been appointed to the post of UK Global Food Security Champion.
more

All impact stories