2017
DOI: 10.1038/ja.2017.9
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Tyropeptins, proteasome inhibitors produced by Kitasatospora sp. MK993-dF2

Abstract: Tyropeptins are new proteasome inhibitors isolated from the culture broth of Kitasatospora sp. MK993-dF2. Tyropeptins permeate cell membranes, inhibit intracellular proteasomes and reduce the degradation of ubiquitinated proteins in mammalian cells. We performed structure-based drug design and structure-activity relationship studies on tyropeptin derivatives to obtain valuable information of derivatives. Among the synthesized tyropeptin derivatives, some boronic acid derivatives exhibited potent antitumor effe… Show more

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Cited by 11 publications
(11 citation statements)
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References 79 publications
(81 reference statements)
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“…Thus, a general reduction of proteasomal activity has an effect on chloroplast protein abundance that is different from the rpn8a mutation. This is not surprising because the 20S proteasome removes damaged proteins under conditions of oxidative stress 9 and inhibition of its activity by MG132 interferes with this important function 25 .…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…Thus, a general reduction of proteasomal activity has an effect on chloroplast protein abundance that is different from the rpn8a mutation. This is not surprising because the 20S proteasome removes damaged proteins under conditions of oxidative stress 9 and inhibition of its activity by MG132 interferes with this important function 25 .…”
Section: Resultsmentioning
confidence: 99%
“…Dried eluates were resuspended in 45 μl of 0.1% (w/v) TFA and 1/3rd of each fraction applied was analyzed by nano-LC-MS/MS using a Orbitrap Fusion Lumos mass spectrometer online-coupled to a nano RSLC HPLC system (both Thermo Scientific). LC separation was performed as described before 25 . Samples were measured in data-dependent acquisition mode using the top speed option (3 s).…”
Section: Methodsmentioning
confidence: 99%
“…With this background in mind, the author carried out synthetic studies on biologically active natural products and their related compounds. In this review, studies on leptolyngbyolides (cytotoxic marine macrolides), 83,84) BE-54017 (V-ATPase inhibitor), 85) tyropeptin (proteasome inhibitor), [86][87][88][89] androprostamine A and resormycin (antiproliferative agents against prostate cancer cells) 90) are not described, although the details can be found in the publications indicated. Synthetic chemistry and natural products have long been friends and provided many opportunities to create medicines which in turn improved public health.…”
Section: Discussionmentioning
confidence: 99%
“…Tyropeptin A and B, isolated from Kitasatospora sp. MK993‐dF2, have also shown potential to inhibit the CT‐L activity of proteasome and reduce growth in prostate cancer cells . Another molecule known as Syringolin A, secreted by Pseudomonas syringae pv.…”
Section: Recent Functional Modulation Of Proteasome: Insights May Ovementioning
confidence: 99%
“…MK993-dF2, have also shown potential to inhibit the CT-L activity of proteasome and reduce growth in prostate cancer cells. 520,521 Another molecule known as Syringolin A, secreted by Pseudomonas syringae pv. syringae inhibits all three proteolytic activities of proteasome.…”
Section: Can Natural Molecules Overcome the Challenges Of Proteasome?mentioning
confidence: 99%