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• W2329016811 endingPage "7553" @default.
• W2329016811 startingPage "7541" @default.
• W2329016811 abstract "Protein kinase C (PKC)-C1 domain targeted regulator development is considered as a potential therapeutic strategy for the treatment of cancer and immunological and other diseases. Efforts are underway to synthesize small molecules to achieve higher specificity for the C1-domain than the natural activator, diacylglycerols (DAGs). In this regard, we conveniently synthesized 4-hydroxy-3-(hydroxymethyl) phenyl ester analogues and measured in vitro C1-domain binding properties. We also investigated different physicochemical properties of the synthesized molecules, including aggregation behavior in aqueous solution and interaction with lipid bilayers, and others with an aim for better understanding of their C1-domain binding properties. The results showed that the membrane-active compounds aggregate in aqueous solution at a reasonably lower concentration and strongly interact with the lipid bilayer. The hydrophilic part of the compounds localize at the bilayer/water interface and accessible for C1-domain binding. Biophysical studies revealed that the hydroxyl, hydroxymethyl, and carbonyl groups and acyl chain length are important for their interaction with the C1-domain. The potent compound showed more than 10-fold stronger binding affinity for the C1-domains than DAG under similar experimental conditions. Therefore, our findings reveal that these ester analogues represent an attractive group of C1-domain ligands that can be further structurally modified to improve their binding and activity." @default.
• W2329016811 created "2016-06-24" @default.
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• W2329016811 date "2014-06-26" @default.
• W2329016811 modified "2023-10-17" @default.
• W2329016811 title "Membrane Interaction and Protein Kinase C-C1 Domain Binding Properties of 4-Hydroxy-3-(hydroxymethyl) Phenyl Ester Analogues" @default.
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• W2329016811 doi "https://doi.org/10.1021/jp5044305" @default.
• W2329016811 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24936745" @default.
• W2329016811 hasPublicationYear "2014" @default.
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