Antifibrotic peptide N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP): opportunities for angiotensin-converting enzyme inhibitor design.
The renin-angiotensin system (RAS) is central to regulation of blood pressure and electrolyte homeostasis.  Angiotensin-converting enzyme (ACE), a key protease in the RAS, has a range of substrates, including N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP). The peptide Ac-SDKP is cleared almost exclusively by ACE, and specifically by the N-domain active site of this enzyme.  N-Acetyl-Ser-Asp-Lys-Pro is a negative regulator of haematopoietic stem cell differentiation and is a potent antifibrotic agent. In this review, the physiological actions of Ac-SDKP are presented, together with the potential clinical usefulness of raising Ac-SDKP levels. This emphasizes the possible opportunity of N-domain-selective ACE inhibitors or ACE-resistant Ac-SDKP analogues for the treatment of fibrosis.
Institute of Infectious Disease and Molecular Medicine, and Division of Medical Biochemistry, University of Cape Town, Cape Town, South Africa.
Ross G
RG
Douglas
Mario R
MR
Ehlers
Edward D
ED
Sturrock
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000933:Antifibrinolytic Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000933:Antifibrinolytic Agents; D009842:Oligopeptides; D007703:Peptidyl-Dipeptidase A; C058504:goralatide
N-acetyl-Ser-Asp-Lys-Pro; angiotensin-converting enzyme inhibition; fibrosis; renin-angiotensin system