18189-19-0Relevant articles and documents
Covalent-Allosteric Inhibitors to Achieve Akt Isoform-Selectivity
Quambusch, Lena,Landel, Ina,Depta, Laura,Weisner, J?rn,Uhlenbrock, Niklas,Müller, Matthias P.,Glanemann, Franziska,Althoff, Kristina,Siveke, Jens T.,Rauh, Daniel
, p. 18823 - 18829 (2019)
Isoforms of protein kinase Akt are involved in essential processes including cell proliferation, survival, and metabolism. However, their individual roles in health and disease have not been thoroughly evaluated. Thus, there is an urgent need for perturbation studies, preferably mediated by highly selective bioactive small molecules. Herein, we present a structure-guided approach for the design of structurally diverse and pharmacologically beneficial covalent-allosteric modifiers, which enabled an investigation of the isoform-specific preferences and the important residues within the allosteric site of the different isoforms. The biochemical, cellular, and structural evaluations revealed interactions responsible for the selective binding profiles. The isoform-selective covalent-allosteric Akt inhibitors that emerged from this approach showed a conclusive structure–activity relationship and broke ground in the development of selective probes to delineate the isoform-specific functions of Akt kinases.
Selection of Alcohols Through Plackett-Burman Design in Lipase-Catalyzed Synthesis of Anthranilic Acid Esters
Babu, C. V. Suresh,Divakar, S.
, p. 49 - 52 (2007/10/03)
Lipase-catalyzed synthesis of esters of anthranilic acid was attempted by employing alcohols of carbon chain-length C1-C18 using Plackett-Burman experimental design. Of the alcohols employed, methanol, decanol, cetyl alcohol, and stearyl alcohols showed 99.9 percent significance. Esterification of anthranilic acid with methanol gave the highest yield at 45.6 percent. This study allows the selection of better alcohols for esterification of anthranilic acid.
