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Together with his UCTcolleague SylvaSchwager and Professor RaviAcharya and Dr Ramanathan Nateshbased at Bath University, Prof Edward Sturrock published the first three-dimensional structure of Angiotensin Converting Enzyme (ACE) in Nature in 2003.
Their breakthrough created enormous interest from the international scientific and medical communities at the time, as over the years numerous high-profile research teams had tried – and failed – to map the enigmatic enzyme.
Armed with a better understanding of the peptide and its interaction with its inhibitors, the team of scientists was then able to begin work on developing a new generation of ACE inhibitor drugs. ACE consists of two parts, the N and C domains, with different functions. Current drugs inhibit both domains. The current generation of ACE inhibitor drugs, which are widely used to treat cardiovascular diseases, such as high blood pressure, heart failure, coronary artery disease, and kidney failure, as well as other related ailments, has unpleasant, and sometimes dangerous, side-effects. These include a persistent dry cough and swelling of the mouth and upper respiratory tract – termed angioedema – which can be life-threatening.
Using the unique knowledge of the three-dimensional structure of ACE, Sturrock and his collaborators have engaged in the design and synthesis of domain-selective ACE inhibitors.
This work will now be pursued by AngioDesign, who purchased Bath University’s interests in the crystal structure patents as well as IP and entered into an assignment agreement for the UCT IP. Although the company has been established in the UK, where funders were able to be found, some of the drug development and discovery activity will continue at UCT.
Prof Edward Sturrock is the lead inventor on 4 patent families relating to the crystal structures of the N and C domains, C-selective ketomethylene ACE inhibitors and C-selective lisinopril-Trp derivatives. The C-domain applications have been granted in 11 European countries, the United States, South Africa and Australia. In addition, a US divisional application has also been granted. The N-domain applications have been granted in 6 European countries, in addition to Australia, the United States and South Africa; a Canadian application is pending as well as a US continuation-in-part.
The Inhibitor 1 family has been granted in Europe (5 countries), the USA, Australia, Canada and South Africa. The Inhibitor 2 family has granted patents in 5 European countries, Australia, Europe, the USA, Canada and South Africa.