Antifibrotic peptide N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP): opportunities for angiotensin-converting enzyme inhibitor design

Abstract

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.

Keywords: N-acetyl-Ser-Asp-Lys-Pro; angiotensin-converting enzyme inhibition; fibrosis; renin-angiotensin system.