Kinins IV pp 405-410 | Cite as

Synthetic Inhibitors of Carboxypeptidase N

  • George H. Fisher
  • James W. Ryan
  • Alfred Chung
  • Thomas H. PlummerJr.
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 198A)


Further to explore the functions of carboxypeptidase N (CPN) in vivo, we undertook two studies to find CPN inhibitors of high potency and relatively long duration of action. In each study we examined for inhibition of hydrolysis of [3H] benzoyl-Ala-Arg using pure bovine serum CPN or human serum. In the first such study we synthesized a series of acyl amino acids and acyl di - and tripeptides containing arginine, lysine or both. All proved to be weak inhibitors (Ki = 10-3 to 10-4 M). Nα-carbamoyl-Arg was the strongest: Ki = 3.5 × 10-5 M.

In the second study we prepared S-acyl (thio ester) derivatives of the highly potent CPN inhibitor 2-mercaptomethyl-3-guanidinoethylthiopropionic acid (2-MGP), as certain S-acyl groups markedly increase the duration of captopril, another mercapto-containing compound. Acetyl-, Boc-phenylalanyl- phenylalanyl-, benzoyl-alanyl-, alanyl-, and Boc-alanyl-2-MGP retained the high potency of 2-MGP in vitro. Although Ala-2-MGP exerted maximum effects in vivo, like those of 2-MGP, the duration of action of Ala-2-MGP was slightly shorter than that of 2-MGP. These results indicate that the mercapto group of 2-MGP can be taken up in some forms of thioester linkage and still retain virtually the full potency of 2-MGP itself. Thus, it appears that a free mercapto function is not essential for the action of 2-MGP.


Angiotensin Converting Enzyme Maleic Anhydride Acyl Derivative Mercapto Group Catalytic Hydrogenolysis 


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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • George H. Fisher
    • 1
  • James W. Ryan
    • 1
  • Alfred Chung
    • 1
  • Thomas H. PlummerJr.
    • 2
  1. 1.Department of MedicineUniversity of Miami School of MedicineMiamiUSA
  2. 2.Center for Laboratories and ResearchNew York State Department of HealthAlbanyUSA

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