Biological Activity of Pepstatins, Pepstanone a and Partial Peptides on Pepsin, Cathepsin D and Renin

Aoyagi, Takaaki; Morishima, Hajime; Nishizawa, Rinzo; Kunimoto, Setsuko; Takeuchi, Tomio; Umezawa, Hamao; Ikezawa, Hiroh

doi:10.7164/antibiotics.25.689

Cited by 105 publications

(39 citation statements)

References 15 publications

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“…E64d is a membrane permeable inhibitor of cathepsins B, H and L, 25,26 and pepstatin A is an inhibitor of cathepsin D and E. 27,28 As is the case with the other lysosomal marker, Lamp1 (Fig. 1), GFP-LC3 was not colocalized with TMR-Dextran in control cells and treatment with protease inhibitors did not affect the GFP-LC3 distribution pattern ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Dissection of the Autophagosome Maturation Process by a Novel Reporter Protein, Tandem Fluorescent-Tagged LC3

2007

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Section: Resultsmentioning

confidence: 99%

Dissection of the Autophagosome Maturation Process by a Novel Reporter Protein, Tandem Fluorescent-Tagged LC3

2007

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“…We also have investigated synthetic renin inhibitors of phosphatidylethanolamine and phos phorylethanolamine (8,9,10,11). One of our derivatives, PE-104 was water soluble and did not inhibit pepsin activity while pepstatins inhibited pepsin and other acid proteases (1). …”

Section: Fig 1 Dose Response Relationship Of N-acetyl-pepstatin In mentioning

confidence: 99%

“…It has been demonstrated that pepstatins isolated from streptmyces inhibit the renin activity and among pepstatins and other renin inhibitory substances, pepstatin A, isovaleryl pentapeptide is known as a most potent renin inhibitor (1,2,3). The solubility of this compound limits application in many studies.…”

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confidence: 99%

Renin Inhibitory Effect of N-Acetyl-Pepstatin

Miyazaki

Okunishi

Komori

et al. 1978

Japanese Journal of Pharmacology

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It has been demonstrated that pepstatins isolated from streptmyces inhibit the renin activity and among pepstatins and other renin inhibitory substances, pepstatin A, isovaleryl pentapeptide is known as a most potent renin inhibitor (1, 2, 3). The solubility of this compound limits application in many studies. In the present work, the renin inhibitory activity of a soluble acid protease inhibitor, N-acetyl-pepstatin, was demonstrated both in vitro and in vivo. N-acetyl-pepstatin was found in a culture filtrate of streptmyces naniwa ensis by Murao and Satoi (4). The chemical structure is N-acetyl-valyl-valyl-4-amino 3-amino-hydroxy-6-methylheptanyl-alanyl-4-amino-3-amino-hydroxy-6-methylheptanic acid;M.W. 644 (5). The same acetyl pentapeptide was also found from strain MD494-Al of streptmyces parvisporogenes by Aoyagi et al (6). N-acetyl-pepstatin is soluble in phosphate buffer at pH 7.4 in concentrations higher than 20 mg/ml.In vitro experiments were carried out using partially purified dog renin and dog renin substrate as described in previous papers (7, 8). One tenth ml of 50 ng angiotensin I equiva lent per hour (Ang-I Eq•hr) of renin and 0.2 ml of 200 ng Ang-I Eq of renin substrate were incubated for 1 hr at 37'C with N-acetyl-pepstatin dissolved in 1/3M phosphate buffer (0.2 mnl, pH 7.4) containing 8 mM EDTA and 0.02% Neomycin. The angiotensin I formed in this mixture was determined by radioimmunoassay. Inhibitory activity of N-acetyl pepstatin was expressed as percentage reduction in the production rate of angiotensin I. Average inhibitions of the renin activity by N-acetyl-pepstatin in a concentration of 10-6 and 10-5 M were 30.9±7.2% and 64.8 -+ 3.2%, respectively (n=8), while those with the same concentration of pepstatin A were 49.7+7.8 % and 89.2+3.7 %, respectively (n=6).Renin inhibitory effect of N-acetyl-pepstatin in vivo was determined by inhibition of

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“…CTSD has an acidic pH optimum, varying from pH 3.5 to 5.0 depending on assay conditions and the substrate used, and its activity is inhibited by pepstatin A [18]. CTSD has been reported to be involved in a number of biologically important processes related to cell proliferation and apoptosis [19][20][21][22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

A replacement of the active-site aspartic acid residue 293 in mouse cathepsin D affects its intracellular stability, processing and transport in HEK-293 cells

Partanen

Storch²,

Löffler

et al. 2003

Biochemical Journal

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The substitution of an active-site aspartic acid residue by asparagine in the lysosomal protease cathepsin D (CTSD) results in a loss of enzyme activity and severe cerebrocortical atrophy in a novel form of neuronal ceroid lipofuscinosis in sheep [Tyynela$ , Sohar, Sleat, Gin, Donnelly, Baumann, Haltia and Lobel (2000) EMBO J. 19, [2786][2787][2788][2789][2790][2791][2792]. In the present study we have introduced the corresponding mutation by replacing aspartic acid residue 293 with asparagine (D293N) into the mouse CTSD cDNA to analyse its effect on synthesis, transport and stability in transfected HEK-293 cells. The complete inactivation of mutant D293N mouse CTSD was confirmed by a newly developed fluorimetric quantification system. Moreover, in the heterologous overexpression systems used, mutant D293N mouse

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Biological Activity of Pepstatins, Pepstanone a and Partial Peptides on Pepsin, Cathepsin D and Renin

Cited by 105 publications

References 15 publications

Dissection of the Autophagosome Maturation Process by a Novel Reporter Protein, Tandem Fluorescent-Tagged LC3

Dissection of the Autophagosome Maturation Process by a Novel Reporter Protein, Tandem Fluorescent-Tagged LC3

Renin Inhibitory Effect of N-Acetyl-Pepstatin

A replacement of the active-site aspartic acid residue 293 in mouse cathepsin D affects its intracellular stability, processing and transport in HEK-293 cells

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