Presenting B-DNA as macromolecular crowding agent to improve efficacy of cytochrome c under various stresses

Shet, Sachin M.; Bharadwaj, Pranav; Bisht, Meena; Pereira, Matheus M.; Thayallath, Sarath Kumar; Lokesh, Veeresh; Franklin, Gregory; Kotrappanavar, Nataraj Sanna; Mondal, Dibyendu

doi:10.1016/j.ijbiomac.2022.06.093

Cited by 9 publications

(16 citation statements)

References 29 publications

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“…26,27 Furthermore, the peaks observed at 1464 cm −1 , 1548 cm −1 and 1574 cm −1 are assigned to the four nucleotide of DNA namely cytosine (in plane vibration of cytosine), adenine (C 7 N vibration of adenine), thymine (C 2 O) and guanine (CO stretch of guanine) indicating the successful immobilization of the ssDNA probe on the electrode surface. 28 Similar FTIR peaks were obtained for the ssDNA/AuNPs/SiNWs-modified electrodes after the introduction of complementary DNA target, confirming the presence of DNA immobilization and hybridization (Fig. 2c).…”

Section: Resultssupporting

confidence: 75%

Strategies in the optimization of DNA hybridization conditions and its role in electrochemical detection of dengue virus (DENV) using response surface methodology (RSM)

et al. 2023

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Section: Resultssupporting

confidence: 75%

Strategies in the optimization of DNA hybridization conditions and its role in electrochemical detection of dengue virus (DENV) using response surface methodology (RSM)

et al. 2023

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“…Above 80°C, the activity drops due to significant denaturation of the protein. 25 A similar trend is observed in the presence of ATP, but the activity extends to approximately a 20-fold increase than for native Cyt c at 70°C. In the case of IL and ATP+IL systems, the denaturation is prevented even up to extremes of 110°C.…”

Section: Resultssupporting

confidence: 67%

“…24 The protein is highly vulnerable to denaturation under prevailing stress conditions such as extreme temperatures, oxidative stress, and proteolytic and chemical denaturants. 25 Recently, a surface modification strategy using quantum dots, metal-organic frameworks, 26 , and DNA was reported to enhance the stability of Cyt c. 25,27 However, the stability of the protein when confined within a hydrotrope system has not yet been reported. Considering the hydrotropism and probability of nano-structuring, 24 the present study aimed to cage Cyt c in ATP and [Cho][Sal] IL-based hydrotropes, and thereby improve the activity and stability of the protein in gentle and harsh environments (such as high temperature, chemical denaturants, protease digestion, and oxidative stress).…”

Section: Introductionmentioning

confidence: 99%

Nano-structured Hydrotrope-Caged Cytochrome c with Boosted Stability in Harsh Environments: A Molecular Insight

Bharadwaj

Sarkar

Bisht

et al. 2023

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Green and nanostructured catalytic media are vital in biocatalysis to attenuate the denaturation tendency of biocatalysts under severe reaction conditions. Hydrotropes with multifaceted physiochemical properties can be envisaged as promising systems for sustainable protein packaging. Herein, the suitability of adenosine-5'-triphosphate (ATP) and cholinium salicylate ([Cho][Sal]) ionic liquid (IL) to form nanostructures and to nanoconfine Cytochrome c (Cyt c) were disclosed envisioning enhancement of stability and activity under multiple stresses. Experimental and computational validations were undertaken to explain nanostructuring phenomenon of ATP and IL, structural organizations of nanoconfined Cyt c, and site-specific interactions that stabilize protein structure. Both, ATP and IL form nanostructures in aqueous media and caged Cyt c via multiple non-specific soft interactions. Remarkably, the engineered molecular nano-cages of ATP (5-10 mM), IL (300 mg/mL), and ATP+IL around Cyt c resulted in 9-72 folds higher peroxidase activity than native Cyt c with exceptionally high thermal tolerance (110 degrees C). The polar interactions mediated by hydrotropes with the cardiolipin binding site of Cyt c well corroborated with the increased peroxidase activity. Further, higher activity trends were observed in the presence of urea, GuHCl, and trypsin without any protein degradation. Specific binding of hydrotropes at highly mobile regions of Cyt c (Omega 40-54 residues) and enhanced H-bonding with Lys and Arg offered excellent stability under extreme conditions. Additionally, ATP effectively counteracted reactive oxygen species (ROS) induced denaturation of Cyt c, which was enhanced by [Sal] counterpart of IL. Overall, this study explored the robustness of nanostructured hydrotropes having a higher potential for protein packaging with improved stability and activity in extreme conditions. Thus, the present work brings out a novel strategy for real-time industrial biocatalysis to protect mitochondrial cells from ROS-instigated apoptosis.

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“…Packaging of cyt c inside B-DNA scaffolds increased its peroxidase activity. Its stability under high temperature, high pH, oxidative stress, and denaturants was also enhanced [ 101 ]. On the other hand, electrostatic adsorption of cyt c on DNA induced self-aggregation of the protein [ 102 ].…”

Section: Approaches For Enhancing Cyt C Thermal St...mentioning

confidence: 99%

Cytochrome c in cancer therapy and prognosis

Pessoa

2022

Bioscience Reports

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Cytochrome c (cyt c) is an electron transporter of the mitochondrial respiratory chain. Upon permeabilization of the mitochondrial outer membrane, cyt c is released into the cytoplasm, where it triggers the intrinsic pathway of apoptosis. Cytoplasmic cyt c can further reach the bloodstream. Apoptosis inhibition is one of the hallmarks of cancer and its induction in tumors is a widely used therapeutic approach. Apoptosis inhibition and induction correlate with decreased and increased serum levels of cyt c, respectively. The quantification of cyt c in the serum is useful in the monitoring of patient response to chemotherapy, with potential prognosis value. Several highly sensitive biosensors have been developed for the quantification of cyt c levels in human serum. Moreover, the delivery of exogenous cyt c to the cytoplasm of cancer cells is an effective approach for inducing their apoptosis. Similarly, several protein-based and nanoparticle-based systems have been developed for the therapeutic delivery of cyt c to cancer cells. As such, cyt c is a human protein with promising value in cancer prognosis and therapy. In addition, its thermal stability can be extended through PEGylation and ionic liquid storage. These processes could contribute to enhancing its therapeutic exploitation in clinical facilities with limited refrigeration conditions. Here, I discuss these research lines and how their timely conjunction can advance cancer therapy and prognosis.

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Presenting B-DNA as macromolecular crowding agent to improve efficacy of cytochrome c under various stresses

Cited by 9 publications

References 29 publications

Strategies in the optimization of DNA hybridization conditions and its role in electrochemical detection of dengue virus (DENV) using response surface methodology (RSM)

Strategies in the optimization of DNA hybridization conditions and its role in electrochemical detection of dengue virus (DENV) using response surface methodology (RSM)

Nano-structured Hydrotrope-Caged Cytochrome c with Boosted Stability in Harsh Environments: A Molecular Insight

Cytochrome c in cancer therapy and prognosis

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