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Macrocyclic Receptors for Biomolecules and Biochemical Sensing
Published in Satish Kumar, Priya Ranjan Sahoo, Violet Rajeshwari Macwan, Jaspreet Kaur, Mukesh, Rachana Sahney, Macrocyclic Receptors for Environmental and Biosensing Applications, 2022
Satish Kumar, Priya Ranjan Sahoo, Violet Rajeshwari Macwan, Jaspreet Kaur, Mukesh, Rachana Sahney
Tweezers are also known to modulate functions of protein-containing lysine residues and protein aggregation behavior causing many diseases. The tweezers 16 (Fig. 7.20) can bind the alkane chains of aliphatic guest molecules inside their cavity by CH–π interactions, while tweezers 17 (Fig. 7.20) can bind aromatic guests via both CH–π and π–π interactions. There are seven different types of 14-3-3 proteins present in human beings which act as adaptor proteins and are involved in many cellular processes. Protein-protein interactions of 14-3-3 proteins regulate the activity of kinase C-Raf and regulate the tumor suppressor protein p53. Among them 14-3-36 contains 17 lysine residues. Molecular tweezers 16e (Fig. 7.20) with negatively charged hydrogen phosphate groups can target these lysine residues and inhibits binding between the 14-3-3 protein (Bier et al. 2013) and two of the partner proteins—a phosphorylated (C-Raf) protein and an unphosphorylated one (ExoS)—in a concentration-dependent manner. Thus macrocyclic structural features can be used as a tool for regulating protein-protein interactions by interference mechanism.
The Use of Fusicoccin as Anticancer Compound
Published in Zulkhair A. Mansurov, Carbon Nanomaterials in Biomedicine and the Environment, 2020
Seitkhan Azat, Almagul R. Kerimkulova, Zulkhair A. Mansurov, Sergazy Adekenov, Gerhard Artmann
Cot-A is a member of the fusicoccane family. Fusicoccanes are small molecules with a typical dicyclopen-ta[a,d]cyclooctane skeleton; 5-8-5 core ring structure [16, 17]. Besides Cot-A there are other fusicoccanes, like Fusicoccin-A (FC) and Ophiobolin (OPH), that differ in the side groups linked to the core structure. FC is produced by the fungus Fusicoccum amygdali Del. This fungus infects peach and almond trees, in which the secreted FC forms a stable complex with the plasma membrane H+-ATP-ase and a 14-3-3 protein [16, 18]. This irreversibly activates the H+-ATPase, and eventually causes the wilting of the tree. The fungus is host specific, but FC is not. It affects the H+-ATPase common to all higher plants and more recently Bunney et al. showed that FC causes the randomization of the left–right axis very early during the Xenopus laevis embryonic development [19]. The mode of action of FC in the embryo development is still unclear, although there are strong indications for the involvement of a 14-3-3 isoform in this organism as well. OPHs are produced by plant pathogenic fungi as well [20]. Currently 23 analogs have been identified, to which various biological activities are ascribed which all are damaging for plants either directly or indirectly [21]. Besides being harmful for plants OPHs possess anti-microbial activities as well as toxicity towards animals and cancer cells. The working mechanism is not completely clear yet and might differ per analog [22, 23]. One of the unique properties of FC is that it stabilizes protein–protein interaction (PPI): viz. the binding between the H+-ATPase and 14-3-3 proteins [24]. PPIs are central to most biological processes—from intercellular communication to programmed cell death—and represent therefore an important class of targets for cancer therapeutics. Hallmark of 14-3-3 protein function is their interaction with numerous proteins, where target phosphorylation is the switch for high affinity binding [25]. Moreover, many cellular processes important in tumor biology—cell cycle control, apoptosis and metastasis—are regulated by 14-3-3 proteins [26]. Therefore, specific targeting of 14-3-3 proteins in tumor cells may be a promising new approach to develop selective drugs. In the present study, we analyzed the effect of the fusicoccanes, FC, OPH-A and OPH-I on cancer cells. We tested their effect on the survival of cell lines derived from various tumor types and showed a synergistic apoptosis induction when FC is combined with IFN-a. Furthermore, we clarified part of the pathway involved in this new combination treatment and showed that the effect of FC is tumor selective since healthy cells are far less sensitive to combined IFN-a/FC treatment.
A critical review for hydrogen application in agriculture: Recent advances and perspectives
Published in Critical Reviews in Environmental Science and Technology, 2023
Renyuan Wang, Xijia Yang, Xunfeng Chen, Xia Zhang, Yaowei Chi, Dan Zhang, Shaohua Chu, Pei Zhou
HRW treatment increased the levels of IAA and GA3 in mung bean seedlings, thus increasing hypocotyl length and root length (Wu, Su, Huang, et al., 2020). In addition, NO may act as a downstream signal molecule in H2 induced adventitious root organogenesis of Cucumber (Cucumis sativus L. cv. Xinchun 4). During adventitious root formation, H2 mediates cell cycle activation through the NO pathway (Zhu et al., 2016). NO could participate in H2 induced adventitious root process by regulating the expression and interaction of PM H+ - ATPase and 14-3-3 protein, which provides more evidence for H2 regulation of cucumber adventitious root development (Li, Huang, et al., 2020).