Prolyl Endopeptidase Inhibitors Derived from Actinomycetes

Kimura, Ken‐ichi; Kanou, Fumiko; Yamashita, Yasushi; Yoshimoto, Tadashi; Yoshihama, Makoto

doi:10.1271/bbb.61.1754

Cited by 11 publications

(9 citation statements)

References 2 publications

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“…nonnitritogenes (IFO14045) and Microbispora indica (IFO14879), but not by Microbispora parva (IFO14043) [8]. Propeptin competitively inhibits the enzyme activity of prolyl endopeptidase (Kiϭ0.7 m M) and also has antimicrobial activity against Mycobacterium phlei IFO3158 (Inhibition zoneϭ12ϳ15 mm at 40 mg/disc) [6,9]. Peptide compounds similar to propeptin have been reported, including anantins (Gly-Asp type) [10,11], RES-701s (Gly-Asp type)…”

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Novel Propeptin Analog, Propeptin-2, Missing Two Amino Acid Residues from the Propeptin C-Terminus Loses Antibiotic Potency

et al. 2007

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A novel inhibitor of prolyl endopeptidase, the propeptin analog propeptin-2 (C 105 H 130 N 24 O 24 ), missing two amino acid residues from the propeptin C-terminus was isolated from the fermentation broth of propeptinproducing Microbispora sp. SNA-115 grown using a large inoculum. It shows the same enzyme inhibition activity as propeptin against prolyl endopeptidase (Kiϭ1.5 m M), but its antimicrobial activity against Mycobacterium phlei is more than 100-fold lower.Keywords propeptin, Microbispora sp., Mycobacterium spp., prolyl endopeptidase Prolyl endopeptidase (PEP; post-proline cleaving enzyme; official name: prolyl oligopeptidase; EC 3.4.21.26) cleaves peptide bonds at the carboxyl side of proline residues and hydrolyzes biologically active peptides containing proline, such as vasopressin and substance P [1,2]. It may also be involved in diseases such as Alzheimer's disease and bipolar affective disorder [3ϳ5]. Meanwhile, effective antituberculosis drugs with novel structures and mechanisms of action have not been developed in over 30 years. Moreover, the increase in Human Immunodeficiency Virus (HIV) and cancer patients has resulted in the spread of opportunistic bacteria, such as the Mycobacterium avium complex (MAC).Propeptin ( Fig. 1(a)

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“…Propeptin inhibits the protease activity of prolyl endopeptidase and the growth of M. phlei [6,9]. Prolyl endopeptidase (Flavobacterium) and substrate (Z-Gly-PropNA) were purchased from Seikagaku Kogyo Co., Ltd.…”

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Novel Propeptin Analog, Propeptin-2, Missing Two Amino Acid Residues from the Propeptin C-Terminus Loses Antibiotic Potency

et al. 2007

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“…Compounds 3 and 4 exhibited in vitro prolyl endopeptidase activity (table 2). N-benzyloxy carbonyl pro-prolinol (Z-pro-prolinol IC 50 ¼ 0.884 AE 0.025 mM) was used as a positive control [19][20][21][22][23][24]. Compound 5 was also isolated previously as a white amorphous substance from S. laureola [4] and has been reported as a synthetic compound [25].…”

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confidence: 99%

A new fatty ester and a new triterpene fromSkimmia laureola

Sultana

Atta-ur-Rahman

Khalid

2008

Natural Product Research

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Aerial parts of Skimmia laureola yielded a new fatty ester, (+)-skimmilaureol (1), and a new triterpene 16-29-dihydroxy, 20-ene cyclolaudenol (2). Five known compounds, namely, O-methyl-cyclolaudenol (3), (R)-7-methoxy-6-(3'-hydroxy-2'R-methoxy-3'-methyl butyl)coumarin (4), (+)-(S)-psi-ribalinine (5), (R)-(+)-ribalinine (6) and methyl isoplatydesmine (7), previously isolated from this plant were subjected to enzymatic bioassays for the first time. Compounds 3 and 4 were found to be prolyl endopeptidase inhibitors with IC(50) 8.21 +/- 0.407 and 39.63 +/- 1.502 microM, respectively, while compounds 5-7 were found to be acetyl-cholinesterase and butyryl-cholinesterase inhibitors with IC(50) 62.46 +/- 1.58, 153.31 +/- 1.9, 74.5 +/- 1.05 and 150.04 +/- 0.45, 12.99 +/- 0.31, 78.3 +/- 1.86 microM, respectively.

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“…Naturally occurring PEP inhibitors are also isolated from sake (traditional Japanese rice wine) [34], ␤-casein [35], wine [36] and proline rich plant proteins [37] contain hydrophobic amino acid residues, and have one or two proline residues in their molecule. Kimura et al [38] isolated four PEP inhibitors from actinomycetes, named propeptin, SNA-8073-B, staurosporine, and enduracidin, and classified into three groups on the basis of their inhibition potency against PEP from a bacterium (Falvobacterium) and a mammal (human placenta). In this study, PEP inhibitory activities of SCOSs were lower than those of PEP inhibition from either synthetic or natural compare with their IC 50 and/or K i values but the results are difficult to compare because PEP inhibitors are not carbohydrate-based inhibitors.…”

Section: Resultsmentioning

confidence: 99%