Antagonist- and inverse agonist-driven interactions of the vitamin D receptor and the constitutive androstane receptor with corepressor protein was written by Lempiainen, Harri;Molnar, Ferdinand;Gonzalez, Manuel Macias;Perakyla, Mikael;Carlberg, Carsten. And the article was included in Molecular Endocrinology in 2005.Electric Literature of C19H12Cl3N3OS This article mentions the following:
Ligand-dependent signal transduction by nuclear receptors (NRs) includes dynamic exchanges of coactivator (CoA) and corepressor (CoR) proteins. Here the authors focused on the structural determinants of the antagonist- and inverse agonist-enhanced interaction of the endocrine NR vitamin D receptor (VDR) and the adopted orphan NR constitutive androstane receptor (CAR) from two species with the CoR NR corepressor. The authors found that the pure VDR antagonist ZK168281 and the human CAR inverse agonist clotrimazole are both effective inhibitors of the CoA interaction of their resp. receptors, whereas ZK168281 resembled more the mouse CAR inverse agonist androstanol in its ability to recruit CoR proteins. Mol. dynamics simulations resulted in comparable models for the CoR receptor interaction domain peptide bound to VDR/antagonist or CAR/inverse agonist complexes. A salt bridge between the CoR and a conserved lysine in helix 4 of the NR is central to this interaction, but also helix 12 was stabilized by direct contacts with residues of the CoR. Fixation of helix 12 in the antagonistic/inverse agonistic conformation prevents an energetically unfavorable free floatation of the C terminus. The comparable mol. mechanisms that explain the similar functional profile of antagonist and inverse agonists are likely to be extended from VDR and CAR to other members of the NR superfamily and may lead to the design of even more effective ligands. In the experiment, the researchers used many compounds, for example, 6-(4-Chlorophenyl)imidazo[2,1-b]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl) oxime (cas: 338404-52-7Electric Literature of C19H12Cl3N3OS).
6-(4-Chlorophenyl)imidazo[2,1-b]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl) oxime (cas: 338404-52-7) belongs to thiazole derivatives. Thiazoles in peptides or their ability to bind proteins, DNA and RNA has led to many synthetic studies and new applications. Thiazole sulfonation occurs only under forcing conditions: the action of oleum at 250 掳C for 3 hours in the presence of mercury(II) sulfate leads to 65% formation of 5-thiazole sulfonic acid.Electric Literature of C19H12Cl3N3OS
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica