36357-77-4

Phosphoramidon, a microbial metabolite, is a specific metalloprotease thermolysin inhibitor with an IC50 of 0.4 μg/mL. Phosphoramidon also inhibits endothelin-converting enzyme (ECE), neutral endopeptidase (NEP), and angiotensin-converting enzyme (ACE) with IC50 values of 3.5, 0.034, and 78 μM, respectively[1][2][3].

ChEBI: A dipeptide isolated from the cultures of Streptomyces tanashiensis.

This glycosyl phosphoramidopeptide (FWfree-acid = 543.51 g/mol; CAS 36357-77-4), also systematically named as N-(a-rhamnopyranosyloxyhydroxyphosphinyl)- L-leucyl-L-tryptophan, is a slow-binding thermolysin inhibitor (Ki = 30 nM). Note: Phosphoramidon is an epimer of talopeptin. Stock 1 mg/mL aqueous solutions of phosphoramidon are stable for one month at –20°C. Target(s): atrolysin A; atrolysin C; bacillolysin; carboxypeptidase C, weakly inhibited; coccolysin; cytosol alanyl aminopeptidase, weakly inhibited; dactylysin; endothelin-converting enzyme; endothelin-converting enzyme 2; fungalysin; gametolysin; granzyme B; Legionella metalloendopeptidase; leucyl aminopeptidase, weakly inhibited; Listeria metalloprotease Mpl; lysine carboxypeptidase, or lysine(arginine) carboxypeptidase; carboxypeptidase N; mycolysin; neprilysin, or enkephalinase, Ki = 0.8 nM; oligopeptidase O; peptidyl-dipeptidase A, or angiotensin I-converting enzyme; pitrilysin, or protease Pi; pseudolysin, or Pseudomonas aeruginosa elastase; pyruvate decarboxylase; thermolysin (27,28,41,43- 53); urethanase; vibriolysin; and Xaa-Pro aminopeptidase, or aminopeptidase P.

Microbial Metabolite

[1] Umezawa S, , et al. A new microbial metabolite phosphoramidon (isolation and structure). Tetrahedron Letters, 1972, 13(1): 97-100.
[2] Suda H, et al. A thermolysin inhibitor produced by actinomycetes: phosphoramidon. The Journal of antibiotics, 1973, 26(10): 621-623.
[3] Kukkola PJ, et al. Differential structure-activity relationships of phosphoramidon analogues for inhibition of three metalloproteases: endothelin-converting enzyme, neutral endopeptidase, and angiotensin-converting enzyme.J CardiovascPharmacol. 1995;26Suppl 3:S65-8. PMID:8587470
[4] Matsumura Y, et al. Phosphoramidon, a metalloproteinase inhibitor, suppresses the hypertensive effect of big endothelin-1. Eur J Pharmacol. 1990 Aug 21;185(1):103-6. DOI:10.1016/0014-2999(90)90216-s
[5] McMahon EG, et al. Phosphoramidon blocks the pressor activity of porcine big endothelin-1-(1-39) in vivo and conversion of big endothelin-1-(1-39) to endothelin-1-(1-21) in vitro. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):703-7. DOI:10.1073/pnas.88.3.703