Protein click chemistry and its potential for medical applications.

A revolution in chemical biology occurred with the introduction of click chemistry. Click chemistry plays an important role in protein chemistry modifications, providing specific, sensitive, rapid, and easy-to-handle methods. Under physiological conditions, click chemistry often overlaps with bioorthogonal chemistry, defined as reactions that occur rapidly and selectively without interfering with biological processes. Click chemistry is used for the posttranslational modification of proteins based on covalent bond formations. With the contribution of click reactions, selective modification of proteins would be developed, representing an alternative to other technologies in preparing new proteins or enzymes for studying specific protein functions in different biological processes. Click-modified proteins have potential in diverse applications such as imaging, labeling, sensing, drug design, and enzyme technology. Due to the promising role of proteins in disease diagnosis and therapy, this review aims to highlight the growing applications of click strategies in protein chemistry over the last two decades, with a special emphasis on medicinal applications.

ROS-Mediated Antitumor Activity, Apoptosis, and Molecular Docking Studies of Platinum(II) Coordination Complexes Bearing 2-(Diphenylphosphino)pyridine Ligands.

Platinum-based drugs have been widely used in cancer treatment. However, their severe side effects have limited their use. So, researchers have been striving to find compounds with fewer side effects and greater efficacy, to overcome these drawbacks. Here, the cytotoxicity of platinum(II) complexes containing 2-(diphenylphosphino)pyridine ligands have been studied on human lung (A549), ovarian (SKOV3), breast (MCF-7) cancer, and normal breast (MCF-10A) cell lines. The most potent compound exhibits a marked cell growth-inhibitory effect against ovarian and lung cancer cells with IC50 values of 9.41 and 5.58 µM, respectively, which were significantly better than that observed for cisplatin (19.02, and 8.64 µM). Additionally, all complexes achieved significantly lower cytotoxicity towards MCF-10A. To investigate the interaction of complexes with DNA, an electrophoresis mobility shift assay was conducted, which indicated that complexes bind to DNA and affect its electrophoretic mobility. An analysis of apoptosis in A549 cells supported the conclusion that they inhibits cell proliferation via induction of apoptosis in a concentration-dependent manner. Molecular docking was also used to investigate the interactions of compounds with different DNA structures. These compounds have the ability to be a suitable pharmaceutical compound with further investigations in the field of cancer research.

Revolutionizing protein hydrolysis in wastewater: Innovative immobilization of metagenome-derived protease in periodic mesoporous organosilica with imidazolium framework.

This research focused on utilizing periodic mesoporous organosilica with imidazolium framework (PMO-IL), to immobilize a metagenome-sourced protease (PersiProtease1), thereby enhancing its functional efficiency and catalytic effectiveness in processing primary proteins found in tannery wastewater. The successful immobilization of enzyme was confirmed through the use of N2 adsorption-desorption experiment, XRD, FTIR, TEM, FESEM, EDS and elemental analytical techniques. The immobilized enzyme exhibited greater stability in the presence of various metal ions and inhibitors compared to its free form. Furthermore, enzyme binding to PMO-IL nanoparticles (NPs) reduced leaching, evidenced by only 11.41 % of enzyme leakage following a 120-min incubation at 80 °C and 6.99 % after 240 min at 25 °C. Additionally, PersiPro@PMO-IL maintained impressive operational consistency, preserving 62.24 % of its activity over 20 cycles. It also demonstrated notable stability under saline conditions, with an increase of 1.5 times compared to the free enzyme in the presence of 5 M NaCl. The rate of collagen hydrolysis by the immobilized protease was 46.82 % after a 15-minute incubation at 60 °C and marginally decreased to 39.02 % after 20 cycles indicative of sustained efficacy without significant leaching throughout the cycles. These findings underscore the effectiveness of PMO-IL NPs as a viable candidate for treating wastewater containing protein.

Synthesis and characterization of MoS2-COOH/gly/Mn nanocomposite as an efficient adsorbent for Ultra-trace determination of trifluralin herbicide.

The world is confronting a severe water crisis. To clean up water from heavy metals, microorganisms, chemicals, and other types of pollutants, nanocomposites have been receiving great attention specifically due to the high surface area affording to work effectually even at low concentrations. In this research, we synthesized a new amino acid-modified MoS2 nanocomposite by chemically immobilizing Mn (II). The synthesized absorbent MoS2-COOH/gly/Mn was identified by thermogravimetric analysis (TGA), nitrogen adsorption measurement, X-ray diffraction (XRD), analysis of energy dispersive X-ray mapping (EDAX and MAP), field emission scanning electron microscopy (FE-SEM), and Fourier Transform Infrared spectrometry (FT-IR). The nanocomposite was employed as an adsorbent through the solid phase microextraction (SPME) method while trifluralin herbicide was chosen as a model compound. For the monitoring of trifluralin molecules, we employed an ion mobility spectrometry apparatus featuring a corona discharge ionization source. The SPME method's effectiveness was examined by investigating the stirring rate and extraction time as two crucial parameters, aiming to achieve trace analysis of trifluralin. Under the optimized condition of the trifluralin extraction, the coefficient (R2) and linear dynamic range (LDR) correlation were obtained at 0.9961 and 0.5-10 µg L-1, respectively. Relative recovery values the described approach were obtained in the span of 96-97% for agricultural wastewater samples. The quantification (LOQ) and limit of detection (LOD) were calculated at 0.5 and 0.15 µg L-1, respectively. The proposed nanocomposite absorbent has the capability to be applied as an efficient material for the extraction of trifluralin herbicide from different solutions.

Potent cyclometallated Pd(II) antitumor complexes bearing α-amino acids: synthesis, structural characterization, DNA/BSA binding, cytotoxicity and molecular dynamics simulation.

A rational approach was adopted to design high-potential metal-based antitumor agents. A series of organometallic Pd(ii) complexes with a general formula of [Pd{κ2(C,C)-[(C6H4-2)PPh2]CH(CO)C6H4Ph-4}{κ2(N,O)}] (N,O = alanine (Pd-A), valine (Pd-V), leucine (Pd-L), l-isoleucine (Pd-I) and phenylalanine (Pd-F)) were prepared by cyclopalladation of the phosphorus ylide, bridge cleavage reaction and subsequent chelation of natural α-amino acids. The complexes were fully identified using IR and multinuclear 1H, 13C, 31P NMR spectroscopic methods. X-ray crystallography exhibited that the Pd(ii) atom is located in a slightly distorted square-planar environment surrounded by C,C-orthometallated phosphorus ylide as well as NO-pendant amino acid functionality. In vitro cytotoxicity evaluation of new cyclometallated Pd(ii) complexes toward a human leukemia (K562) cancer cell line indicated promising results. The highest cytotoxic activity was discovered in the case of phenylalanine (CH2C6H5). IC50 values of this complex on a panel of human tumor cell lines representative of liver (HepG2), breast (SKBR-3), and ovarian (A2780-Resistance/Sensitive) cancers also indicated promising antitumor effects in comparison with standard cisplatin. The binding interaction ability of the phenylalanine-containing orthopalladated complex, as the most efficient compound, with calf-thymus deoxyribonucleic acid (CT-DNA) and bovine serum albumin (BSA) was investigated. UV-Vis spectroscopy, competitive emission titration, and circular dichroism (CD) techniques demonstrated the intercalative binding of the Pd(ii) complex with DNA. Molecular docking studies also fully agreed with the experimental data. Examination of the reactivity towards the protein BSA revealed that the static quenching mechanism of BSA intrinsic fluorescence by the Pd(ii) complex with a binding constant (Kb) of ∼105 is indicative of the high affinity of the complex. The competitive binding experiment using site markers with definite binding sites demonstrated that the hydrophobic cavities of site I (subdomain IIA) are responsible for the bimolecular interaction between protein BSA and the complex. Molecular docking studies effectively confirmed the significance of hydrophobic interactions in Pd(ii)-BSA binding. The results of this study could greatly contribute to exploring new potent metal-based anticancer drugs.

trans-Platinum(II) Thionate Complexes: Synthesis, Structural Characterization, and in†vitro Biological Assessment as Potent Anticancer Agents.

A series of Pt(II) complexes trans-[Pt(PPh2 allyl)2 (κ1 -S-SR)2 ], 1, PPh2 allyl=allyldiphenylphosphine, SR=pyridine-2-thiol (Spy, 1 a), 5-(trifluoromethyl)-pyridine-2-thiol (SpyCF3 -5, 1 b), pyrimidine-2-thiol (SpyN, 1 c), benzothiazole-2-thiol (Sbt, 1 d), benzimidazole-2-thiol (Sbi, 1 e), were synthesized. They were characterized by NMR, HR ESI-MS, and X-ray crystallography. Treatment of human cancer cell lines (A549, SKOV3, MCF-7) with these complexes resulted in promising antitumor effects in comparison with cisplatin. These compounds showed suitable selectivity between tumorigenic and non-tumorigenic (MCF-10 A) cell lines. Analyses of cell cycle progression and apoptosis were conducted for 1 a, the most cytotoxic compound, to screen dose/time response and to study the antiproliferative mechanism. An electrophoresis mobility shift assay was performed to assess the direct interaction of 1 a with DNA and the strong genotoxic ability was indicated through the comet assay method.