Endothelin converting enzymes

Endothelin. The endothelin (ET) peptide family (50) comprises thiee peptides ET-1 (133), ET-2 (134), and ET-3 (135). ET-1, the most abundant, is a 21-amino acid peptide. A 203-amino acid peptide piecuisoi, piepioET, is cleaved after translation by endopeptidases to form a 38-amino acid proET which is converted to active ET by a putative endothelin-converting enzyme (ECE). ET-3 differs from ET-1 and ET-2 by sis amino acids. 

Endothelins. Table 2 Properties of the different isoforms of endothelin-converting enzymes... 

AHF acute heart failure, CHF chronic heart failure, CRF chronic renal failure, NEP neutral endopeptidase, ECE endothelin converting enzyme, PAH pulmonary arterial hypertension. 

Yanagisawa H, Hammer RE, Richardson JA et al (2000) Disruption of ECE-1 and ECE-2 reveals a role for endothelin-converting enzyme-2 in murine cardiac development. J Clin Invest 105 1373-1382... 

MA M13 M13.002 Endothelin-converting enzyme 1 Drug target in hypertension. 

Endothelial Nitric Oxide Synthase (eNOS) Endothelin Converting Enzyme Endothelins Endothelium... 

EBV Epstein-Barr virus EC Endothelial cell ECD Electron capture detector ECE Endothelin-converting enzyme E-CEF Eosinophil cytotoxicity enhancing fector... 

Further susceptibilities of the nonapeptide are shown in Fig. 6.34. Thus, the Pro7-Phe8 bond is also cleaved by neprilysin (EC 3.4.24.11) and endothelin-converting enzyme (EC 3.4.24.71) [149][165]. The C-terminal residue is susceptible to cleavage by several carboxypeptidases, particularly carboxypeptidase N. Thimet oligopeptidase (EC 3.4.24.15) is also able to act on bradykinin, which is cleaved at the Phe5-Ser6 bond [144],... 

M. V. Hoang, A. J. Turner, Novel Activity of Endothelin-Converting Enzyme Hydrolysis of Bradikinin , Biochem. J. 1997, 327, 23-26. 

Hofstra, R. M. W., Valdenaire, O., Arch, E., et al. (1999) A loss-of-function mutation in the endothelin-converting enzyme 1 (ECE-1) associated with Hirschsprung disease, cardiac defects, and autonomic dysfunction. Am. J. Hum. Genet. 64, 304-308. 

Eckman, E.A., Watson, M., Marlow, L., Sambamurti, K., Eckman, C.B. (2003) Alzheimer s disease P-amyloid peptide is increased in mice deficient in endothelin-converting enzyme. J. Biol. Chem., 278, 2081-2084. 

Eckman, E.A., Adams, S.K., Troendle, F.J., et al. (2006) Regulation of steady-state beta-amyloid levels in the brain by neprilysin and endothelin-converting enzyme but not angiotensin-converting enzyme. J. Biol. Chem., 281, 30471-30478. 

The endothelin system can be blocked with receptor antagonists and drugs that block endothelin-converting enzyme. Endothelin or ETB receptors can be blocked selectively, or both can be blocked with nonselective - antagonists. 

The formation of endothelins can be blocked by inhibiting endothelin-converting enzyme with phosphoramidon. Phosphoramidon is not specific for endothelin-converting enzyme, but several more selective inhibitors are now available for research. Although the therapeutic potential of these drugs appeared similar to that of the endothelin receptor antagonists (see below), their use has been eclipsed by endothelin antagonists. 

Systemic administration of endothelin receptor antagonists or endothelin-converting enzyme inhibitors causes vasodilation and decreases arterial pressure in humans and experimental animals. Intra-arterial administration of the drugs also causes slow-onset forearm vasodilation in humans. These observations provide evidence that the endothelin system participates in the regulation of vascular tone, even under resting conditions. The activity of the system is higher in males than in females. It increases with age, an effect that can be counteracted by regular aerobic exercise. 

The sterol sulfate, halistanol disulfate B (544) was isolated from a South African Pachastrella sp. The structure and stereochemistry of compound 544 were established mainly by interpretation of spectral data. Halistanol disulfate B (544) was active in the endothelin converting enzyme (ECE) assay at a micromolar concentration [451]. Three sterol trisulfates (545-547) have been isolated from the sponges Trachyopsis halichondrioides and Cymbastela coralliophila [452]. 

In the total synthesis of ( )-WS75644B 360, a biaryl endothelin converting enzyme inhibitor, pyrone 357 derived from kojic acid was converted to pyridone 358 by reaction with concentrated ammonium hydroxide in a sealed flask at 90 °C. The resulting pyridine was subsequently converted to 2,4,5-trisubstituted pyridine 359 and ultimately elaborated to complete the total synthesis (Scheme 54) <1997TL1297>. 

Angiotensin I converting enzyme Acquired immunodeficiency syndrome Aspartic protease inhibitor Bowman Birk protease inhibitor protein Chymotrypsin Cysteine protease inhibitor Endothelin-converting enzyme Elastase... 

EGE, endothelin-converting enzyme EGMOX, cytochrome P450-dependent... 

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