Eurystatins A and B, new prolyl endopeptidase inhibitors. I. Taxonomy, production, isolation and biological activities.

Abstract

EurystatinsA and B, were isolated from the cultured broth of Streptomyces eurythermus R353-21. They showed specific and potent inhibitory activity against prolyl endopeptidase and did not showantimicrobial activity. No lethal toxicity was observed for the two compoundsafter ip administration in mice at 200mg/kg.

Synthesis of the Cyclic Peptidic Protease Inhibitor Eurystatin A Using Acyl Cyano Phosphorane Methodology

“…In the absence of an authentic sample of eurystatin A, we relied on the identity of the 1 H NMR spectrum of our synthetic product with the corresponding spectrum of the natural material supplied by Bristol-Myers Squibb Pharmaceutical Research Institute. In addition, the 13 C NMR, IR, MS, HRMS, mp, optical rotation, elemental analysis, and TLC were in agreement with the published data 1b…”

“…Eurystatins A ( 1a ) and B ( 1b ), isolated from Streptomyces eurythermus R353-21, are potent inhibitors of the serine protease prolyl endopeptidase (PED). Their structures incorporate ( S )-3-amino-2-oxobutanoic acid, leucine, and ornithine residues in a cyclic framework.…”

A Prolyl Endopeptidase-Inhibiting Benzofuran Dimer from Polyozellus multiflex

“…[7][8][9][10]23 Many pyrrolidine derivatives such as Z-Pro-Prolinal and JTP-4819 have been synthesized as potent PEP inhibitors. 15 On the other hand, staurosporine, 16 poststatin, 17 eurystatin, 18 lipohexin, 19 propeptin, 20 and SNA-8073-B 21 were isolated from microbial sources. Plant-derived flavonoids containing a catechol ring 22 and tannins with a pyrogallol moiety 23 have also been reported to effectively inhibit the activity of PEP.…”

A β-Secretase (BACE1) Inhibitor Hispidin from the Mycelial Cultures ofPhellinus linteus

“…Z-Pro-prolinal was synthesized according to the method of Bakker et al [11] and used as a positive control. The PEP activity and the inhibition percent of all samples were determined according to the previously reported method [12]. Chymotrypsin, trypsin, and elastase were assayed according to the protocol described in the references [13], [14], [15] using N-benzoyl-L-Arg-pNA, N-benzoyl-L-Tyr-pNA, and N-succinyl-Ala-Ala-Ala-pNA as substrates, respectively.…”