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1.
Kessler BM Tortorella D Altun M Kisselev AF Fiebiger E Hekking BG Ploegh HL Overkleeft HS 《Chemistry & biology》2001,8(9):913-929
BACKGROUND: The 26S proteasome is responsible for most cytosolic proteolysis, and is an important protease in major histocompatibility complex class I-mediated antigen presentation. Constitutively expressed proteasomes from mammalian sources possess three distinct catalytically active species, beta1, beta2 and beta5, which are replaced in the gamma-interferon-inducible immunoproteasome by a different set of catalytic subunits, beta1i, beta2i and beta5i, respectively. Based on preferred cleavage of short fluorogenic peptide substrates, activities of the proteasome have been assigned to individual subunits and classified as 'chymotryptic-like' (beta5), 'tryptic-like' (beta2) and 'peptidyl-glutamyl peptide hydrolyzing' (beta1). Studies with protein substrates indicate a far more complicated, less strict cleavage preference. We reasoned that inhibitors of extended size would give insight into the extent of overlapping substrate specificity of the individual activities and subunits. RESULTS: A new class of proteasome inhibitors, considerably extended in comparison with the commonly used fluorescent substrates and peptide-based inhibitors, has been prepared. Application of the safety catch resin allowed the generation of the target compounds using a solid phase protocol. Evaluation of the new compounds revealed a set of highly potent proteasome inhibitors that target all individual active subunits with comparable affinity, unlike the other inhibitors described to date. Modification of the most active compound, adamantane-acetyl-(6-aminohexanoyl)(3)-(leucinyl)(3)-vinyl-(methyl)-sulfone (AdaAhx(3)L(3)VS), itself capable of proteasome inhibition in living cells, afforded a new set of radio- and affinity labels. CONCLUSIONS: N-terminal extension of peptide vinyl sulfones has a profound influence on both their efficiency and selectivity as proteasome inhibitors. Such extensions greatly enhance inhibition and largely obliterate selectivity towards the individual catalytic activities. We conclude that for the interaction with larger substrates, there appears to be less discrimination of different substrate sequences for the catalytic activities than is normally assumed based on the use of small peptide-based substrates and inhibitors. The compounds described here are readily accessible synthetically, and are more potent inhibitors in living cells than their shorter peptide vinyl sulfone counterparts. 相似文献
2.
Theoretical and Mathematical Physics - We study the eikonal approximation of the total cross section for the scattering of two unpolarized particles and obtain an approximate formula in the case... 相似文献
3.
The multiple hadron production in the events induced by the heavy primary quarks in e+e- annihilation is reconsidered with account of corrected experimental data. A new value for the multiplicity in bb̄ events
is presented on the basis of pQCD estimates. 相似文献
4.
R. Kopp A. Argento A. C. Benvenuti D. Bollini G. Bruni T. Camporesi M. Cribier J. Cvach N. G. Fadeev J. Feltesse I. A. Golutvin M. Goossens G. Heiman D. Jamnik Y. T. Kiryushin V. S. Kisselev M. Klein V. G. Krivokhizhin V. V. Kukhtin W. Lohmann U. Meyer-Berkhout A. Milsztajn L. Monari F. L. Navarria W. D. Nowak A. Ouraou L. Piemontese P. Rich-Hennion Y. Sacquin I. A. Savin G. Smadja G. I. Smirnov A. Staude K. M. Teichert R. Tirler G. Todorova P. Todorov P. Verrecchia G. Vesztergombi M. Virchaux A. G. Volodko R. Voss J. Zacek Č. Zupančič BCDMS Collaboration 《Zeitschrift fur Physik C Particles and Fields》1985,28(2):171-174
5.
Gerjan de Bruin Bo Tao Xin Dr. Marianne Kraus Dr. Mario van der Stelt Prof. Dr. Gijsbert A. van der Marel Dr. Alexei F. Kisselev Prof. Dr. Christoph Driessen Dr. Bogdan I. Florea Prof. Dr. Herman S. Overkleeft 《Angewandte Chemie (International ed. in English)》2016,55(13):4199-4203
Proteasomes are therapeutic targets for various cancers and autoimmune diseases. Constitutively expressed proteasomes have three active sites, β1c, β2c, and β5c. Lymphoid tissues also express the immunoproteasome subunits β1i, β2i, and β5i. Rapid and simultaneous measurement of the activity of these catalytic subunits would assist in the discovery of new inhibitors, improve analysis of proteasome inhibitors in clinical trials, and simplify analysis of subunit expression. In this work, we present a cocktail of activity‐based probes that enables simultaneous gel‐based detection of all six catalytic human proteasome subunits. We used this cocktail to develop specific inhibitors for β1c, β2c, β5c, and β2i, to compare the active‐site specificity of clinical proteasome inhibitors, and to demonstrate that many hematologic malignancies predominantly express immunoproteasomes. Furthermore, we show that selective and complete inhibition of β5i and β1i is cytotoxic to primary cells from acute lymphocytic leukemia (ALL) patients. 相似文献
6.
The small curvature option of the Randall-Sundrum model with two branes is considered which has almost continuous spectrum of low-mass Kaluza-Klein gravitons. It is shown that gravity effects related with these excitations can be detected in double diffractive events at the LHC and in inclined air showers induced by interactions of cosmic neutrinos with atmospheric nucleons at ultra-high energies. 相似文献
7.
A. V. Kisselev 《Physics of Atomic Nuclei》2010,73(6):996-1014
Theories featuring extra spatial dimensions are considered, and scattering cross sections in such theories are estimated.
The role of high-energy cosmic neutrinos in discovering effects associated with extra dimensions is emphasized. Neutrino detectors,
their sensitivity to diffuse neutrino fluxes, and expected limits on the fundamental gravity scale are described. 相似文献
8.
Bogdan I. Florea Martijn Verdoes Nan Li Wouter A. van der Linden Paul P. Geurink Hans van den Elst Tanja Hofmann Arnoud de Ru Peter A. van Veelen Keiji Tanaka Katsuhiro Sasaki Shigeo Murata Hans den Dulk Jaap Brouwer Ferry A. Ossendorp Alexei F. Kisselev Herman S. Overkleeft 《Chemistry & biology》2010,17(8):795-801
9.
Miklukho O. V. Kisselev A. Yu. Amalsky G. M. Andreev V. A. Barsov S. G. Gavrilov G. E. Zhdanov A. A. Izotov A. A. Ilyin D. S. Kozlenko N. G. Kravchenko P. V. Maysuzenko D. A. Murzin V. I. Novinskiy D. V. Shvedchikov A. V. 《Physics of Atomic Nuclei》2020,83(3):431-441
Physics of Atomic Nuclei - The secondary proton polarization and differential cross sections of the ( $$p,p^{\prime}$$ ) inelastic reaction on nuclei $${}^{9}$$ Be and $${}^{90}$$ Zr at the initial... 相似文献
10.
A.V. Kisselev V.A. Petrov R.A. Ryutin 《The European Physical Journal C - Particles and Fields》2003,26(4):597-600
Quark mass effects are analyzed at high Q2 in the current fragmentation region of DIS. It is found that the linear combination F
2
-2.75F
c
2 scales at large Q2 and small x. We obtained a lower bound for the ratio F
c
2/F
2
which lies very close to the data from HERA.
Received: 14 January 2002 / Revised version: 9 October 2002 Published online: 9 December 2002
RID="a"
ID="a" e-mail: ryutin@th1.ihep.su 相似文献