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Antifibrotic peptide N ‐acetyl‐Ser‐Asp‐Lys‐Pro (Ac‐ SDKP ): Opportunities for angiotensin‐converting enzyme inhibitor design
Author(s) -
Douglas Ross G,
Ehlers Mario R,
Sturrock Edward D
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12062
Subject(s) - chemistry , angiotensin converting enzyme , enzyme , renin–angiotensin system , peptide , angiotensin ii , pharmacology , protease , biochemistry , receptor , endocrinology , biology , blood pressure
Summary 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.