27688-87-5Relevant academic research and scientific papers
Autophagy targeting protein degradation technology and application thereof
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Paragraph 0080; 0093-0094; 0128; 0135-0136, (2020/12/29)
The invention relates to the technical field of targeted protein degradation, discloses an autophagy targeted protein degradation technology and application thereof, and particularly relates to an autophagy targeted chimeric body, application thereof and
P62/SQSTM1/Sequestosome-1 is an N-recognin of the N-end rule pathway which modulates autophagosome biogenesis
Cha-Molstad, Hyunjoo,Yu, Ji Eun,Feng, Zhiwei,Lee, Su Hyun,Kim, Jung Gi,Yang, Peng,Han, Bitnara,Sung, Ki Woon,Yoo, Young Dong,Hwang, Joonsung,McGuire, Terry,Shim, Sang Mi,Song, Hyun Dong,Ganipisetti, Srinivasrao,Wang, Nuozhou,Jang, Jun Min,Lee, Min Jae,Kim, Seung Jun,Lee, Kyung Ho,Hong, Jin Tae,Ciechanover, Aaron,Mook-Jung, Inhee,Kim, Kwang Pyo,Xie, Xiang-Qun,Kwon, Yong Tae,Kim, Bo Yeon
, (2017/08/01)
Macroautophagy mediates the selective degradation of proteins and non-proteinaceous cellular constituents. Here, we show that the N-end rule pathway modulates macroautophagy. In this mechanism, the autophagic adapter p62/SQSTM1/Sequestosome-1 is an N-recognin that binds type-1 and type-2 N-terminal degrons (N-degrons), including arginine (Nt-Arg). Both types of N-degrons bind its ZZ domain. By employing three-dimensional modeling, we developed synthetic ligands to p62 ZZ domain. The binding of Nt-Arg and synthetic ligands to ZZ domain facilitates disulfide bond-linked aggregation of p62 and p62 interaction with LC3, leading to the delivery of p62 and its cargoes to the autophagosome. Upon binding to its ligand, p62 acts as a modulator of macroautophagy, inducing autophagosome biogenesis. Through these dual functions, cells can activate p62 and induce selective autophagy upon the accumulation of autophagic cargoes. We also propose that p62 mediates the crosstalk between the ubiquitin-proteasome system and autophagy through its binding Nt-Arg and other N-degrons.
Asymmetric synthesis of (2S)-1-(3,4-dihydroxyphenoxy)-3-(3,′4′- dimethoxyphenoxy) ethylamino-2-propanol hydrochloride (RO363)
Narsaiah, Akkirala Venkat
, p. 1897 - 1901 (2007/10/03)
Enantiomerically pure (S)-RO363 was synthesized by using (R,R) Salen Co(III) complex for the resolution of terminal epoxide. The hydrolytic kinetic resolution process was carried out at room temperature in excellent enantioselectivity. The method can be a
Synthesis and β-adrenoceptor agonist properties of (±)-1-(3',4'- dihydroxyphenoxy)-3-(3',4'-dimethoxyphenyl) ethylamino-2-propanol hydrochloride, (±)-RO363.HCl, and the (2S)-(-)-isomer
Iakovidis, Dimitri,Louis, Simon N. S.,Rezmann, Linda A.,Colagrande, Felicia,Nero, Tracy L.,Jackman, Graham P.,Louis, William J.
, p. 539 - 548 (2007/10/03)
The synthesis of (±)-1-(3',4'-dihydroxyphenoxy)-3-(3',4'- dimethoxyphenyl)ethylamino-2-propanol hydrochloride, (±)RO363.HCl, and the (2S)-(-)-isomer is described for the first time. The binding affinities for (±)-RO363.HCl, (2S)-(-)-RO363.HCl and a number of well known β-adrenoceptor agonists for transfected humanβ1,-, β2- and β3-adrenoceptors expressed in Chinese hamster ovary cells have been determined and compared with the functional potencies in rat atria (β1) and trachea (β2). The results indicate that both (±)-RO363 and (2S)-(-)-RO363 are selective for the human and rat β1-adrenoceptors. The (2S)-(-)-isomer of RO363, as expected, has a higher binding affinity for the human and functional potency for rat β- adrenoceptor subtypes than the racemate. However, in contrast to the catecholamines and formoterol, the functional potency of the racemic mixture and its (-)-enantiomer are not significantly different from their binding affinity, suggesting that they are examples of partial agonists with sufficient intrinsic activity to produce full agonist responses.
BIS-PHENOXYPROPANOLAMINES
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, (2008/06/13)
Bis-phenoxypropanolamine derivatives are prepared. These compounds have β-adrenergic stimulant activity particularly as selective bronchodilators.
