Fatty acid-binding proteins

Xu, He-Li; Diolintzi, Anastasia; Storch, Judith

doi:10.1097/mco.0000000000000600

Cited by 38 publications

(17 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the last synthesis step, acylation with stearic acid was carried out in order to introduce a hydrophobic end group to the molecule. This end group allows for locating the polymer drug conjugate close to cell membranes . To investigate the influence of the PEG chain length on the behavior of our structures, we further synthesized oligopeptoids containing polymeric PEG with a molecular weight of 2000 g mol –1 as side chains.…”

Section: Introductionmentioning

confidence: 99%

Solid-Phase Synthesis as a Tool to Create Exactly Defined, Branched Polymer Vectors for Cell Membrane Targeting

Elter,

Liščáková,

Moravec

et al. 2024

Macromolecules

View full text Add to dashboard Cite

Modern drug formulations often require, besides the active drug molecule, auxiliaries to enhance their pharmacological properties. Tailor-made, biocompatible polymers covalently connected to the drug molecule can fulfill this function by increasing its solubility, reducing its toxicity, and guiding it to a specific target. If targeting membrane-bound proteins, localization of the drug close to the cell membrane and its target is beneficial to increase drug efficiency and residence time. In this study, we present the synthesis of highly defined, branched polymeric structures with membrane-binding properties. One to three hydrophilic poly(ethylene oxide) or poly(2-ethyloxazoline) side chains were connected via a peptoid backbone using a two-step iterative protocol for solid-phase peptoid synthesis. Additional groups, e.g., a hydrophobic anchor for membrane attachment, were introduced. Due to the nature of solid-phase synthesis, the number and order of the side chains and additional units can be precisely defined. The method proved to be versatile for the generation of multifunctional, branched polymeric structures of molecular weights up to approximately 7000 g mol −1 . The behavior of all compounds towards biological membranes and cells was investigated using liposomes as cell membrane models, HEK293 and U251-MG cell lines, and red blood cells, thereby demonstrating their potential value as drug auxiliaries with cell membrane affinity.

show abstract

Section: Introductionmentioning

confidence: 99%

Solid-Phase Synthesis as a Tool to Create Exactly Defined, Branched Polymer Vectors for Cell Membrane Targeting

Elter,

Liščáková,

Moravec

et al. 2024

Macromolecules

View full text Add to dashboard Cite

show abstract

“…Under physiological conditions, CD36 expression is low in hepatocytes, but CD36 is highly induced with lipid overload and is activated by transcription factors ( 26 ). Once FFAs enter hepatocytes, they are bound and transported by fatty acid binding protein 1 (FABP1), and functional PPREs identified within the FABP1 promoter are regulated by PPARα based on nutritional conditions through protein–protein interactions ( 15 , 27 – 29 ). Carnitine palmitoyltransferase 1A (CPT1A), which transports FFAs into mitochondria, is localized in the outer mitochondrial membrane and acts as a β-oxidation rate-limiting enzyme regulated by PPARα ( 15 , 30 ).…”

Section: Introductionmentioning

confidence: 99%

Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

Lian

Zhang

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

IntroductionThe study aimed to explore the association of serum 25(OH)D3 and hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) patients and to determine whether the effect of vitamin D (VD) is mediated by activation of the peroxisome proliferator-activated receptor α (PPARα) pathway.MethodsThe study contained a case-control study, in vivo and in vitro experiments. A case-control study was conducted to compare serum parameters between NAFLD patients and controls and to evaluate the association of 25(OH)D3 and NAFLD. In vivo study, male Wistar rats were randomly divided into control and model groups, fed a standard chow diet and a high-fat diet (HFD), respectively, for 7 weeks to generate an NAFLD model. Then, the rats were treated with VD and a PPARα antagonist (MK886) for 7 weeks. Tissue and serum were collected and assessed by biochemical assays, morphological analysis, histological analysis, and western blot analysis. In vitro, HepG2 cells were incubated with oleic acid (OA) to induce steatosis, which was evaluated by staining. HepG2 cells were pretreated with MK886 followed by calcitriol treatment, and differences in lipid metabolism-related proteins were detected by western blot.ResultsNAFLD patients were characterized by impaired liver function, dyslipidemia, and insulin resistance. Serum 25(OH)D3 was negatively associated with alanine aminotransferase (ALT) in NAFLD. VD deficiency was a risk factor for patients with no advanced fibrosis. Adequate VD status (25(OH)D3 >20 ng/mL) had a protective effect in patients after adjustment for confounding variables. NAFLD rats showed hyperlipidemia with severe hepatic steatosis, systematic inflammation, and lower serum 25(OH)D3. VD treatment ameliorated hepatic steatosis both in NAFLD rats and OA-induced HepG2 cells. Further, MK886 inhibited the anti-steatosis effect of VD.ConclusionThe study revealed that an adequate VD level may act as a protective factor in NAFLD and that VD may alleviate hepatic steatosis via the PPARα signaling pathway.

show abstract

“…Protein engineering refers to the process of optimizing protein sequences for enhanced physical (e.g., thermal stability, solubility, and complex stoichiometry), chemical (e.g., reactivity, substrate specificity, selectivity, and substrate scope), biological, and pharmaceutical functions. Typical strategies in protein engineering include directed evolution, − gene shuffling/recombination, , site-directed mutagenesis, , and protein truncation and fusion. , Enabled by protein engineering, researchers can create enzymes to accelerate low-efficiency − or even new-to-nature reactions, , develop peptides with targeted therapeutic effects, , innovate diagnostic tools for early stage cancer detection, − and advance our understanding of fundamental life processes. , …”

Section: Introductionmentioning

confidence: 99%

Mutexa: A Computational Ecosystem for Intelligent Protein Engineering

Yang,

Shao,

Jiang

et al. 2023

J. Chem. Theory Comput.

View full text Add to dashboard Cite

Protein engineering holds immense promise in shaping the future of biomedicine and biotechnology. This Review focuses on our ongoing development of Mutexa, a computational ecosystem designed to enable "intelligent protein engineering". In this vision, researchers will seamlessly acquire sequences of protein variants with desired functions as biocatalysts, therapeutic peptides, and diagnostic proteins through a finely-tuned computational machine, akin to Amazon Alexa's role as a versatile virtual assistant. The technical foundation of Mutexa has been established through the development of a database that combines and relates enzyme structures and their respective functions (e.g., IntEnzyDB), workflow software packages that enable high-throughput protein modeling (e.g., EnzyHTP and LassoHTP), and scoring functions that map the sequence-structure−function relationship of proteins (e.g., EnzyKR and DeepLasso). We will showcase the applications of these tools in benchmarking the convergence conditions of enzyme functional descriptors across mutants, investigating protein electrostatics and cavity distributions in SAM-dependent methyltransferases, and understanding the role of nonelectrostatic dynamic effects in enzyme catalysis. Finally, we will conclude by addressing the future steps and fundamental challenges in our endeavor to develop new Mutexa applications that assist the identification of beneficial mutants in protein engineering.

show abstract

Fatty acid-binding proteins

Cited by 38 publications

References 68 publications

Solid-Phase Synthesis as a Tool to Create Exactly Defined, Branched Polymer Vectors for Cell Membrane Targeting

Solid-Phase Synthesis as a Tool to Create Exactly Defined, Branched Polymer Vectors for Cell Membrane Targeting

Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

Mutexa: A Computational Ecosystem for Intelligent Protein Engineering

Contact Info

Product

Resources

About