Background: Previous studies found that Vitamin E (VE) could recruit protein kinase B (Akt1) to the membrane by targeting its unconventional lipid-binding site, which led to the dephosphorylation of Akt1 at Ser473, eventually deactivating the enzyme.
Methods: A series of VE-like compounds with varying types and lengths of the linker groups are designed to study the VE-driven membrane recruitment of Akt1 using a combined molecular docking and molecular dynamics (MD) simulation approach.
Results: We find that the linker groups with only one methylene linker and multiple hydrogen bond donors are optimal for achieving a balance between binding to the protein and partitioning into the membrane to form a stable protein-ligand-membrane ternary complex. These polar linkers are found to form stable hydrogen bonds with the lipid head groups during the MD simulations, which turns out critical for ensuring that the chromanol ring of the VE-like compounds resides above the membrane surface to fully engage in the protein.
Conclusions: Our results reveal the molecular determinants of the linker groups for VE derivatives' ability to anchor Akt1 to the membrane.
General Significance: These findings will facilitate the design of membrane interfacial compounds to recruit specific proteins to the membrane to modulate the protein function.
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http://dx.doi.org/10.1016/j.bbagen.2020.129655 | DOI Listing |
Sci Rep
January 2025
Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre U. 9, 1092, Budapest, Hungary.
Microtiter-plate-based systems are unified platforms of high-throughput experimentation (HTE). These polymeric devices are used worldwide on a daily basis-mainly in the pharmaceutical industry-for parallel syntheses, reaction optimization, various preclinical studies and high-throughput screening methods. Accordingly, laboratory automation today aims to handle these commercially available multiwell plates, making developments focused on their modifications a priority area of modern applied research.
View Article and Find Full Text PDFPolymers (Basel)
January 2025
Department of Materials Science and Engineering, Iowa State University, Ames, IA 50011, USA.
This review examines the recent advancements and unique properties of polymer-inorganic hybrid materials formed through coordination bonding (Class II hybrids), which enable enhanced functionality and stability across various applications. Here, we categorize these materials based on properties gained through complexation, focusing on electrical conductivity, thermal stability, photophysical characteristics, catalytic activity, and nanoscale self-assembly. Two major synthetic approaches to making these hybrids include homogeneous and heterogeneous methods, each with distinct tradeoffs: Homogeneous synthesis is straightforward but requires favorable mixing between inorganic and polymer species, which are predominantly water-soluble complexes.
View Article and Find Full Text PDFBiomolecules
January 2025
Department of Chemistry, Molecular Basis of Disease, Petit Science Center, Georgia State University, 100 Piedmont Avenue SE, Atlanta, GA 30303, USA.
Donor acceptor (D-π-A) fluorophores containing a donor unit and an acceptor moiety at each end connected by a conjugated linker gained attention in the last decade due to their conjugated system and ease of tunability. These features make them good candidates for various applications such as bioimaging, photovoltaic devices and nonlinear optical materials. Upon excitation of the D-π-A fluorophore, intramolecular charge transfer (ICT) occurs, and it polarizes the molecule resulting in the 'push-pull' system.
View Article and Find Full Text PDFBiochemistry
January 2025
Department of Chemistry, Texas A&M University, College Station, Texas 77843, United States.
is the leading cause of food poisoning in Europe and North America. The exterior surface of this bacterium is encased by a capsular polysaccharide that is attached to a diacyl glycerol phosphate anchor via a poly-Kdo (3-deoxy-d--oct-2-ulosinic acid) linker. In the HS:2 serotype of NCTC 11168, the repeating trisaccharide consists of d-ribose, -acetyl-d-glucosamine, and d-glucuronate.
View Article and Find Full Text PDFNanomaterials (Basel)
January 2025
School of Sciences and Humanities, Nazarbayev University, Astana 010000, Kazakhstan.
Doxorubicin (DOX) is one of the most widely used chemotherapy drugs in the treatment of both solid and liquid tumors in patients of all age groups. However, it is likely to produce several side effects that include doxorubicin cardiomyopathy. Nanoparticles (NPs) can offer targeted delivery and release of the drug, potentially increasing treatment efficiency and alleviating side effects.
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