67844-32-0Relevant academic research and scientific papers
Structure-Based Design of β5c Selective Inhibitors of Human Constitutive Proteasomes
Xin, Bo-Tao,De Bruin, Gerjan,Huber, Eva M.,Besse, Andrej,Florea, Bogdan I.,Filippov, Dmitri V.,Van Der Marel, Gijsbert A.,Kisselev, Alexei F.,Van Der Stelt, Mario,Driessen, Christoph,Groll, Michael,Overkleeft, Herman S.
supporting information, p. 7177 - 7187 (2016/08/24)
This work reports the development of highly potent and selective inhibitors of the β5c catalytic activity of human constitutive proteasomes. The work describes the design principles, large hydrophobic P3 residue and small hydrophobic P1 residue, that led to the synthesis of a panel of peptide epoxyketones; their evaluation and the selection of the most promising compounds for further analyses. Structure-activity relationships detail how in a logical order the β1c/i, β2c/i, and β5i activities became resistant to inhibition as compounds were diversified stepwise. The most effective compounds were obtained as a mixture of cis- and trans-biscyclohexyl isomers, and enantioselective synthesis resolved this issue. Studies on yeast proteasome structures complexed with some of the compounds provide a rationale for the potency and specificity. Substitution of the N-terminus in the most potent compound for a more soluble equivalent led to a cell-permeable molecule that selectively and efficiently blocks β5c in cells expressing both constitutive proteasomes and immunoproteasomes.
Living copolymerization of ethylene with norbornene catalyzed by bis(pyrrolide-imine) titanium complexes with MAO
Yoshida, Yasunori,Mohri, Jun-Ichi,Ishii, Sei-Ichi,Mitani, Makoto,Saito, Junji,Matsui, Shigekazu,Makio, Haruyuki,Nakano, Takashi,Tanaka, Hidetsugu,Onda, Mitsuhiko,Yamamoto, Yukari,Mizuno, Akira,Fujita, Terunori
, p. 12023 - 12032 (2007/10/03)
Bis(pyrrolide-imine) Ti complexes in conjunction with methylalumoxane (MAO) were found to work as efficient catalysts for the copolymerization of ethylene and norbornene to afford unique copolymers via an addition-type polymerization mechanism. The catalysts exhibited very high norbornene incorporation, superior to that obtained with Me2Si(Me4Cp)(N-tert-Bu)TiCl 2 (CGC). The sterically open and highly electrophilic nature of the catalysts is probably responsible for the excellent norbornene incorporation. The catalysts displayed a marked tendency to produce alternating copolymers, which have stereoirregular structures despite the C2 symmetric nature of the catalysts. The norbornene/ethylene molar ratio in the polymerization medium had a profound influence on the molecular weight distribution of the resulting copolymer. At norbornene/ethylene ratios larger than ca. 1, the catalysts mediated room-temperature living copolymerization of ethylene and norbornene to form high molecular weight monodisperse copolymers (Mn > 500 000, Mw/Mn 13C NMR spectroscopic analysis of a copolymer, produced under conditions that gave low molecular weight, demonstrated that the copolymerization is initiated by norbornene insertion and that the catalyst mostly exists as a norbornene-last-inserted species under living conditions. Polymerization behavior coupled with DFT calculations suggested that the highly controlled living polymerization stems from the fact that the catalysts possess high affinity and high incorporation ability for norbornene as well as the characteristics of a living ethylene polymerization though under limited conditions (Mn 225 000, Mw/Mn 1.15, 10-s polymerization, 25 °C). With the catalyst, unique block copolymers [i.e., poly(ethylene-co-norbornene)1-b-poly(ethylene-co-norbornene) 2, PE-b-poly(ethylene-co-norbornene)] were successfully synthesized from ethylene and norbornene. Transmission electron microscopy (TEM) indicated that the PE-b-poly(ethylene-co-norbornene) possesses high potential as a new material consisting of crystalline and amorphous segments which are chemically linked.
