Hitting on the move: Targeting intrinsically disordered protein states of the MDM2-p53 interaction was written by Neochoritis, Constantinos G.;Atmaj, Jack;Twarda-Clapa, Aleksandra;Surmiak, Ewa;Skalniak, Lukasz;Kohler, Lisa-Maria;Muszak, Damian;Kurpiewska, Katarzyna;Kalinowska-Tluscik, Justyna;Beck, Barbara;Holak, Tad A.;Domling, Alexander. And the article was included in European Journal of Medicinal Chemistry in 2019.Category: alcohols-buliding-blocks This article mentions the following:
Intrinsically disordered proteins are an emerging class of proteins without a folded structure and currently disorder-based drug targeting remains a challenge. p53 is the principal regulator of cell division and growth whereas MDM2 consists its main neg. regulator. The MDM2-p53 recognition is a dynamic and multistage process that amongst other, employs the dissociation of a transient α-helical N-terminal ”lid” segment of MDM2 from the proximity of the p53-complementary interface. Several small mol. inhibitors have been reported to inhibit the formation of the p53-MDM2 complex with the vast majority mimicking the p53 residues Phe19, Trp23 and Leu26. Recently, the authors have described the transit from the 3-point to 4-point pharmacophore model stabilizing this intrinsically disordered N-terminus by increasing the binding affinity by a factor of 3. Therefore, the authors performed a thorough SAR anal., including chiral separation of key compound which was evaluated by FP and 2D NMR. Finally, p53-specific anticancer activity towards p53-wild-type cancer cells was observed for several representative compounds In the experiment, the researchers used many compounds, for example, (2,4-Dichlorophenyl)methanol (cas: 1777-82-8Category: alcohols-buliding-blocks).
(2,4-Dichlorophenyl)methanol (cas: 1777-82-8) belongs to alcohols. A strong base can deprotonate an alcohol to yield an alkoxide ion (R―O−). For example, sodamide (NaNH2), a very strong base, abstracts the hydrogen atom of an alcohol. Secondary alcohols are easily oxidized without breaking carbon-carbon bonds only as far as the ketone stage. No further oxidation is seen except under very stringent conditions.Category: alcohols-buliding-blocks
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts