Search

Chemical modifications to Cytosine bases are among the most studied epigenetic markers and their detection in the human genome plays a crucial role in gaining more insights about gene regulation, prognosis of genetic disorders and unraveling genetic inheritance patterns. The Cytosine methylated at the 5th position and oxidized derivatives thereof generated in the demethylation pathways, perform separate and unique epigenetic functions in an organism. As the presence of various Cytosine modifications is associated with diverse diseases, including cancer, there has been a strong focus on developing methods, both chemical and alternative approaches, capable of detecting these modifications at a single‐base resolution across the entire genome. In this comprehensive review, we aim to consolidate the various chemical methods and understanding their chemistry that have been established to date for the detection of various Cytosine modifications. [ABSTRACT FROM AUTHOR]

Copper can act as a double-edged sword as it can cause fatal diseases when in excess or shortage. Precise control of copper homeostasis is maintained by a complex machinery inside cells. To overcome imbalances in copper concentration, we have developed a simple system to control the cellular copper concentration by using a photocaged chelator and light. This photocaged chelator allowed us to control cellular copper concentration in a spatiotemporal manner. [ABSTRACT FROM AUTHOR]

Stable spirodiazaselenurane and spirodiazatellurane are prepared by oxidative spirocyclization of the corresponding diaryl selenide and telluride and are structurally characterized. The studies have shown that the tellurium compounds are more effective as glutathione peroxidase (GPx) has mimicked than their selenium counterparts due to the fast oxidation of the tellurium center in the presence of peroxide and the involvement of an efficient redox cycle between the telluride and telluroxide intermediate.

Halogenated nucleosides can be incorporated into the newly synthesized DNA of replicating cells and therefore are commonly used in the detection of proliferating cells in living tissues. Dehalogenation of these modified nucleosides is one of the key pathways involved in DNA repair mediated by the uracil-DNA glycosylase. Herein, we report the first example of a selenium-mediated dehalogenation of halogenated nucleosides. We also show that the mechanism for the debromination is remarkably different from that of deiodination and that the presence of a ribose or deoxyribose moiety in the nucleosides facilitates the deiodination. The results described herein should help in understanding the metabolism of halogenated nucleosides in DNA and RNA. [ABSTRACT FROM AUTHOR]

The type 1 iodothyronine deiodinase (1D-1) in liver and kidney converts the L-thyroxine ( T4), a prohormone, by outer-ring (5′) deiodination to biologically active 3,3′,5-triiodothyronine ( T3) or by inner-ring (5) deiodination to inactive 3,3′,5′-triiodothronine ( rT3). Sulfate conjugation is an important step in the irreversible inactivation of thyroid hormones. While sulfate conjugation of the phenolic hydroxyl group stimulates the 5-deiodination of T4 and T3, it blocks the 5′-deiodination of T4. We show that thyroxine sulfate ( T4S) undergoes faster deiodination as compared to the parent thyroid hormone T4 by synthetic selenium compounds. It is also shown that ID-3 mimics, which are remarkably selective to the inner-ring deiodination of T4 and T3, changes the selectivity completely when T4S is used as a substrate. From the theoretical investigations, it is observed that the strength of halogen bonding increases upon sulfate conjugation, which leads to a change in the regioselectivity of ID-3 mimics towards the deiodination of T4S. It has been shown that these mimics perform both the 5′- and 5-ring deiodinations by an identical mechanism. [ABSTRACT FROM AUTHOR]

Iodothyronine deiodinases (IDs) are mammalian selenoenzymes that catalyze the conversion of thyroxine (T4) to 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) by the outer- and inner-ring deiodination pathways, respectively. These enzymes also catalyze further deiodination of T3 and rT3 to produce a variety of di- and monoiodo derivatives. In this paper, the deiodinase activity of a series of peri-substituted naphthalenes having different amino groups is described. These compounds remove iodine selectively from the inner-ring of T4 and T3 to produce rT3 and 3,3'-diiodothyronine (3,3'-T2), respectively. The naphthyl-based compounds having two selenols in the peri-positions exhibit much higher deiodinase activity than those having two thiols or a thiol-selenol pair. Mechanistic investigations reveal that the formation of a halogen bond between the iodine and chalcogen (S or Se) and the peri-interaction between two chalcogen atoms (chalcogen bond) are important for the deiodination reactions. Although the formation of a halogen bond leads to elongation of the C-I bond, the chalcogen bond facilitates the transfer of more electron density to the C-I σ* orbitals, leading to a complete cleavage of the C-I bond. The higher activity of amino-substituted selenium compounds can be ascribed to the deprotonation of thiol/selenol moiety by the amino group, which not only increases the strength of halogen bond but also facilitates the chalcogen-chalcogen interactions. [ABSTRACT FROM AUTHOR]

Chemical modifications to Cytosine bases are among the most studied epigenetic markers and their detection in the human genome plays a crucial role in gaining more insights about gene regulation, prognosis of genetic disorders and unraveling genetic inheritance patterns. The Cytosine methylated at the 5 th position and oxidized derivatives thereof generated in the demethylation pathways, perform separate and unique epigenetic functions in an organism. As the presence of various Cytosine modifications is associated with diverse diseases, including cancer, there has been a strong focus on developing methods, both chemical and alternative approaches, capable of detecting these modifications at a single-base resolution across the entire genome. In this comprehensive review, we aim to consolidate the various chemical methods and understanding their chemistry that have been established to date for the detection of various Cytosine modifications., (© 2024 Wiley-VCH GmbH.)

SARS-CoV-2 main protease (M pro /3CL pro ) is a crucial target for therapeutics, which is responsible for viral polyprotein cleavage and plays a vital role in virus replication and survival. Recent studies suggest that 2-phenylbenzisoselenazol-3(2 H )-one (ebselen) is a potent covalent inhibitor of M pro , which affects its enzymatic activity and virus survival. Herein, we synthesized various ebselen derivatives to understand the mechanism of M pro inhibition by ebselen. Using ebselen derivatives, we characterized the detailed interaction mechanism with M pro . We discovered that modification of the parent ebselen inhibitor with an electron-withdrawing group (NO 2 ) increases the inhibition efficacy by 2-fold. We also solved the structure of an M pro complex with an ebselen derivative showing the mechanism of inhibition by blocking the catalytic Cys145 of M pro . Using a combination of crystal structures and LC-MS data, we showed that M pro hydrolyzes the new ebselen derivative and leaves behind selenium (Se) bound with Cys145 of the catalytic dyad of M pro . We also described the binding profile of ebselen-based inhibitors using molecular modeling predictions supported by binding and inhibition assays. Furthermore, we have also solved the crystal structure of catalytically inactive mutant H41N-M pro , which represents the inactive state of the protein where the substrate binding pocket is blocked. The inhibited structure of H41N-M pro shows gatekeeper residues in the substrate binding pocket responsible for blocking the substrate binding; mutation of these gatekeeper residues leads to hyperactive M pro ., Competing Interests: The authors declare no competing financial interest., (© 2022 American Chemical Society.)

Precise control of the self-assembly of selected components within complex mixtures is a challenging goal whose realization is important for fabricating novel nanomaterials. Herein we show that by decorating the surfaces of metallic nanoparticles with differently substituted azobenzenes, it is possible to modulate the wavelength of light at which the self-assembly of these nanoparticles is induced. Exposing a mixture of two types of nanoparticles, each functionalized with a different azobenzene, to UV or blue light induces the selective self-assembly of only one type of nanoparticles. Irradiation with the other wavelength triggers the disassembly of the aggregates, and the simultaneous self-assembly of nanoparticles of the other type. By placing both types of azobenzenes on the same nanoparticles, we created unique materials ("frustrated" nanoparticles) whose self-assembly is induced irrespective of the wavelength of the incident light., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Halogenated nucleosides can be incorporated into the newly synthesized DNA of replicating cells and therefore are commonly used in the detection of proliferating cells in living tissues. Dehalogenation of these modified nucleosides is one of the key pathways involved in DNA repair mediated by the uracil-DNA glycosylase. Herein, we report the first example of a selenium-mediated dehalogenation of halogenated nucleosides. We also show that the mechanism for the debromination is remarkably different from that of deiodination and that the presence of a ribose or deoxyribose moiety in the nucleosides facilitates the deiodination. The results described herein should help in understanding the metabolism of halogenated nucleosides in DNA and RNA., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)