Structure-Based Design of Domain-Selective Angiotensin-Converting Enzyme Inhibitors

  • Ross G. Douglas
  • Edward D. Sturrock


Cardiovascular disease (CVD) affects a significant proportion of the African adult population and requires new and improved strategies for the effective control of this disease. Angiotensin-converting enzyme (ACE) is a two-domain zinc metallopeptidase that plays a central role in the renin-angiotensin-aldosterone system and has thus been identified as a promising therapeutic target in the treatment of CVD and its major risk factor, hypertension. Numerous ACE inhibitors have been developed that are used clinically but tend to result in adverse drug events, such as persistent cough and life-threatening angioedema. Research over the previous two decades has allowed for an improved understanding of the function of the two ACE domains and thus provides a basis for the design of second-generation, domain-selective ACE inhibitors. This chapter reviews our current understanding of ACE biochemistry, first-generation ACE inhibitors and the utilised technologies and progress towards the development of such inhibitors that could be useful in the treatment of hypertension and lung fibrosis.


Idiopathic Pulmonary Fibrosis Residue Contribution Domain Active Site Functional Group Contribution AngII Production 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Angiotensin-converting enzyme




Adverse drug event


Angiotensin I


Angiotensin II


Angiotensin 1-7


Angiotensin type 1 receptor


Angiotensin type 2 receptor




Bradykinin-potentiating factor


Carboxypeptidase A


Cardiovascular disease


keto-ACE Phe inhibitor


keto-ACE Trp


Lisinopril Trp


Protein Data Bank (


Renin-angiotensin-aldosterone system


Testis angiotensin-converting enzyme


World Health Organisation


Zinc Metalloprotease Research Group


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© Springer Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Division of Medical Biochemistry, Institute of Infectious Disease and Molecular MedicineUniversity of Cape TownObservatory, Cape TownSouth Africa

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