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Enlarging the ligand binding pocket by reduction of
2020-10-30

Enlarging the ligand-binding pocket by reduction of the size of the residue F435 switched DES to an agonist indicating that F435 is involved in mediating the antagonistic effect of DES (Fig. 7E) [13]. The conformation of the smaller side chain of L435 was either not altered by DES or was too small t
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br Materials and Methods br Results br Discussion
2020-10-30

Materials and Methods Results Discussion The spatial properties of receptor-ligand interactions can influence receptor activation and signal propagation, but studying this phenomenon requires the development of systems capable of recapitulating complex biophysical traits. In this study, we
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While previously reported optimizations on compound
2020-10-30

While previously reported optimizations on AG-120 synthesis focused on the phenyl ring A () and substituents on isoxazole ring, other alternatives to replace isoxazole ring were never explored. Herein, we propose to replace the isoxazole with its bioisosteric substituted phenyl ring B () to explore
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The importance of EBI for B cell
2020-10-30

The importance of EBI2 for B cell function was first suggested by the dramatic upregulation of this receptor in EBV-transformed cholecystokinin receptor and further inferred from its regulation in activated and GC B cells (Birkenbach et al., 1993, Glynne et al., 2000, Shaffer et al., 2000). An invo
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br Acknowledgement br Introduction Human dihydroorotate dehy
2020-10-30

Acknowledgement Introduction Human dihydroorotate dehydrogenase (hDHODH), a flavin-dependent mitochondrial enzyme involved in de novo Dihydrotestosterone biosynthesis, is a validated therapeutic target for the treatment of autoimmune diseases such as rheumatoid arthritis and cancer [1], [2],
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There exists a glucose residue in the structure of
2020-10-30

There exists a glucose residue in the structure of 5. Acid hydrolysis (Supplementary data) followed by TLC comparison with the reference compound as well as GC–MS analysis (l-cysteine methyl ester hydrochloride derivative: tR=22.22min for glucose residue of 5 and 22.46min for the reference compound)
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Compounds were prepared via the
2020-10-30

Compounds were prepared via the routes shown in , varying the sequence of reactions to install the thiazole or the phenyl ring at the end of the synthesis (pyridyl examples were prepared using similar chemistry). The aminothiazole building blocks were prepared as shown in . 5-Aminothiazole was prep
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The structures of the set of
2020-10-30

The structures of the set of pyrazoles of are contained in the supplied with this manuscript. Acknowledgments Prostaglandin D (PGD) is known to bind with high affinity to two G protein-coupled seven-transmembrane receptors DP1 and DP2. The latter receptor, also known as CRTH2 (chemoattractant
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Although the presence of at least one
2020-10-30

Although the presence of at least one triple helix domain is typically the collagen signature, collagens are modular proteins composed of a succession of collagenous (COL) and non-collagenous domains (NC) that are both involved in collagen functions and in receptor binding. COL domains are linked by
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SB 747651A dihydrochloride Nearly years ago the first
2020-10-30

Nearly 60years ago, the first two SB 747651A dihydrochloride which catalyze the phosphorylation of proteins were discovered [1]. Protein phosphorylation was originally identified as a regulatory mechanism for the control of glycogen metabolism. Today it is clear that protein phosphorylation regulat
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br Introduction Myotonic dystrophy dystrophia myotonica DM i
2020-10-30

Introduction Myotonic dystrophy (dystrophia myotonica, DM) is an autosomal dominant disorder and the most common form of inherited muscular dystrophy in adults [1]. DM is characterised by a wide range of symptoms, including myotonia, progressive muscle loss, cataracts, cardiac conduction defects,
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Damage of PE HD due to both mechanisms is usually
2020-10-30

Damage of PE-HD due to both mechanisms is usually considered to emerge from a local stress concentration in the material, leading to the initiation of a crack, which subsequently propagates further through the material, and finally leads to macroscopic failure. In this process, crack growth occurs o
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While oxysterols were most extensively studied for its
2020-10-29

While oxysterols were most extensively studied for its potent ability to mediate feedback regulation of cholesterol biosynthesis, some early investigations showed that the enzymes involved in its syntheses were highly upregulated in macrophages and dendritic cells—an indication of possible roles in
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br TRIM TIF A RNF TRIM contains
2020-10-29

TRIM24 (TIF1A, RNF82) TRIM24 contains a RING-both B-boxes-coiled coil conserved structure at the N-terminus with bromo and PHD domains prior to C-terminal end (Fig. 3). This transcriptional intermediary factor is well studied in the context of transcriptional activation of nuclear receptor via ac
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External factors such as protein partners can also activate
2020-10-29

External factors, such as protein partners, can also activate DUBs by either reinforcing the stimulatory effects of intramolecular factors or by other means. The intramolecular activation of the USP7 CD by its HUBL domain is allosterically potentiated by external factor GMP synthase (GMPS), which co
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