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MOF-based Electrochemical Sensors for Protein Detection
Published in Ram K. Gupta, Tahir Rasheed, Tuan Anh Nguyen, Muhammad Bilal, Metal-Organic Frameworks-Based Hybrid Materials for Environmental Sensing and Monitoring, 2022
Yang Liu, Juanhua Zhou, Shiyu Zhang, Hongye Wang
Protein kinase is a kind of enzyme that catalyzes the process of protein phosphorylation. Its activity is closely related to various diseases. Therefore, the detection of protein kinase activity in clinical diagnosis can help diagnosis. Song et al. proposed a low fouling and highly sensitive electrochemical sensor for T4 polynucleotide kinase (PNK) detection based on zwitterionic peptide and self-sacrificial Fe-MOF [67]. The zwitterionic peptide could be assembled into antifouling layers and the Fe-MOF formed Prussian blue (PB) after reacting with K4Fe(CN)6. Thus, the biosensor prevented the adsorption of nonspecific proteins and had a high sensitivity. Another kinase, protein tyrosine kinase-7 (PTK7) could also be detected by an electrochemical biosensor based on Zn-MOF-on-Zr-MOF architecture [33]. In addition to electrochemical biosensors, photoelectrochemical biosensors attracted lots of interest as well. Our team developed a highly sensitive photoelectrochemical biosensor for the detection of protein kinase A (PKA) by Ru(bpy)32+ loaded UiO-66 (Ru(bpy)32+@UiO-66) [44]. UiO-66 not only increased the load of Ru(bpy)32+ but also provided a large number of phosphorylated kemptide binding sites. Therefore, the biosensor achieved high sensitivity and fast response.
Synapses
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
We next consider some enzymes and proteins that play important roles in second-messenger systems. A second messenger can activate a protein kinase (PKA), which is an enzyme that has catalytic subunits and regulatory subunits. In the inactive state the catalytic subunits are inhibited by the regulatory subunits, but this inhibition is removed by the binding of a second messenger, which allows the catalytic subunits to phosphorylate target proteins (Section 1.1.2). In the phosphorylation of a target protein, a phosphate group from an ATP molecule is substituted for an OH– group in one of the amino acid side chains of the target protein. Phosphorylation alters the structural conformation of a protein, thereby activating it or modifying its function. The phosphorylated, or target, proteins can perform many functions, including gating of ion channels, regulation of metabolism of glycogen, sugar, and lipids; or expression of specific genes. Protein kinases can also be activated not by second messengers but by other protein kinases in a cascade of protein kinases. The amino acids that are commonly phosphorylated are serine, threonine, and tyrosine.
Small-Molecule Inhibitors Targeting Receptor Tyrosine Kinases in Cancer
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Mohammad Hojjat-Farsangi, Gholamreza Khamisipour
The term “oncogenic addiction” was coined by Weinstein (Weinstein, 2000) in 2000 and demonstrated that cancer cells might show addiction to an oncogenic signaling molecule or pathway to sustain tumor activity such as survival and proliferation. Various enzymes such as tyrosine/serine/threonine kinases, are known to be crucial for the process of oncogenesis. Kinases are protein enzymes that phosphorylate and transfer a phosphate group from adenosine 3 phosphates (ATP) to special amino acid residues, including tyrosine, serine, or threonine. Phosphorylation of proteins is one of the most vital events that regulate cellular activities in a precise way. Overall, phosphorylation of oncoproteins is a necessary phenomenon for tumor cells regulation and activation (Tsai and Nussinov, 2013).
Investigating orthodontic tooth movement: challenges and future directions
Published in Journal of the Royal Society of New Zealand, 2020
Fiona A. Firth, Rachel Farrar, Mauro Farella
Cells sense mechanical strain and relay the mechanical stimulus to other cells via the process of mechanotransduction. Integrins are well-suited to be mechanotransducers because they are mechanoreceptors that are linked to the cytoskeleton. Integrin receptors are thought to bind to extracellular matrix (ECM) ligands, transmitting signals across the cell membrane. Regulation of cellular functions is achieved via this sequence of events, as well as by the recruitment of kinase enzymes, which also assist in the regulation of protein activity by phosphorylation (Wang and Thampatty 2006). It has been proposed that bone cells, particularly osteocytes, play an essential role during this phase as mechanosensors (Tan et al. 2006; Henneman et al. 2008; Krishnan and Davidovitch 2009). Osteocytes are connected via a 3D network of cell processes, through which interstitial fluid flows in response to bone loading (Burger and Klein-Nulend 1999).
Zinc(II) derivatives of N, O containing Schiff bases: synthesis, characterization, computational and biological studies
Published in Journal of Coordination Chemistry, 2023
Saadia Batool, Anham Zafar, Muhammad Athar, Mehwish Mehmood, Muhammad Nawaz Tahir, Ihsan-Ul Haq, Sayed Sikander Azam
Protein kinase inhibition assay has been performed for I1–I9 and 1–9 using surfactin as positive control showing maximum bald zone of 30.3 mm and DMSO as a negative control; the data are tabulated in Table 7. Among the free ligands, I4 and I6 displayed significant bald zones of 16 and 14 mm, respectively, whereas I5 and I7 showed clear zones of 14 mm. Among the complexes, only 1–3 possessed significant bald zones of 18, 20, and 14 mm; 2 exhibits highest bald inhibition zone because of its naphthalene group that facilitates the pi-electron resonance. Bald and clear inhibition zones close to 20 mm indicate moderate inhibitory potential and cytotoxicity, respectively. Basically, the strain of eukaryotic Streptomyces 85E is used to perform protein kinase inhibition activity, as it delivered a clear demonstration of cytotoxic nature as well as anticancer potential of all tested compounds. Main function of protein kinases (PTKs) is to normalize the biological activity of proteins via phosphorylation of amino acids by using ATP as phosphate source. Protein undergoes a conformational change from inactive to an active state, and the inhibitors of these enzymes are particularly involved in discontinuing their function to stop the spread of cancerous cells [46]. The presented data for ligands and their metal complexes may act as scaffold for drug development projects in future. The protein kinase inhibition potential for all screened compounds is depicted in Figure S6 as supplementary file.
Bio-medical potential of chalcone derivatives and their metal complexes as antidiabetic agents: a review
Published in Journal of Coordination Chemistry, 2021
Tyrosine phosphatases are named after their phosphate group removing function from phosphorylated tyrosine residues. Originally, phosphorylation of proteins which is a post-translational alteration is executed by kinases (enzymes) to synchronize the cell life [37]. Similarly, tyrosine kinase aids the insulin receptors present on the membrane to metabolize carbohydrates and fat from the bloodstream [38]. So, insulin receptor tyrosine kinase, which is present on the membrane, acts as the mediator to communicate the biological effects of insulin. Insulin receptor membrane has two subunits, ligand binding subunit and tyrosine kinase subunit. Initially, ligand binding subunit senses the insulin followed by activation of the tyrosine binding subunit prompting its autophosphorylation. This domino effect of two subunits initiates the phosphorylation of downstream insulin receptor substrate proteins. This pathway propagates the insulin signal leading to intake of glucose from the bloodstream to the cell [39] which is shown in Figure 1. But, tyrosine phosphatase plays the role of negative regulator and perturbs this pathway by removing the phosphate groups from crucial tyrosine residues instigating the resistance of receptors to insulin [39]. In addition to this, thiol group present on the cysteine residue’s active site of the protein tyrosine phosphatase (PTP1B) attacks as a nucleophile on enzyme employing the covalent catalysis and supervening in the formation of thiophosphoryl enzyme intermediate. So, the PTP1B activity can be completely aborted by substituting the cysteine residue [40]. Based on research, it is clinically approved that inhibition of PTP1B can serve as the target for therapeutic intercessions in type 2 diabetes mellitus [41].