The nanocarrier with efficient encapsulation ability is potentially applicable for drug delivery, biosensing, biocatalytic, and diagnostic tools.Addressing intracellular targets is a challenging task that requires potent molecular transporters capable to deliver various cargos. Herein, we report the synthesis of hydrophobic macrocycles composed of both amino acids and peptoid monomers. The cyclic tetramers and hexamers were assembled in a modular approach using solid as well as solution phase techniques. To monitor their intracellular localization, the macrocycles were attached to the fluorophore Rhodamine B. Most molecular transporters were efficiently internalized by HeLa cells and revealed a specific accumulation in mitochondria without the need for cationic charges. The data will serve as a starting point for the design of further cyclic peptoid-peptide hybrids presenting a new class of highly efficient, versatile molecular transporters.Coronaviruses are responsible for multiple pandemics and millions of deaths globally, including the current pandemic of coronavirus disease 2019 (COVID-19). Development of antivirals against coronaviruses, including the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) responsible for COVID-19, is essential for containing the current and future coronavirus outbreaks. https://www.selleckchem.com/products/tg003.html SARS-CoV-2 proteases represent important targets for the development of antivirals because of their role in the processing of viral polyproteins. 3-Chymotrypsin-like protease (3CLpro) is one such protease. The cleavage of SARS-CoV-2 polyproteins by 3CLpro is facilitated by a Cys145-His41 catalytic dyad. We here characterized the catalytic roles of the cysteine-histidine pair for improved understanding of the 3CLpro reaction mechanism, to inform the development of more effective antivirals against Sars-CoV-2. The catalytic dyad residues were substituted by site-directed mutagenesis. All substitutions tested (H41A, H41D, H41E, C145A, and C145S) resulted in a complete inactivation of 3CLpro, even when amino acids with a similar catalytic function to that of the original residues were used. The integrity of the structural fold of enzyme variants was investigated by circular dichroism spectroscopy to test if the catalytic inactivation of 3CLpro was caused by gross changes in the enzyme secondary structure. C145A, but not the other substitutions, shifted the oligomeric state of the enzyme from dimeric to a higher oligomeric state. Finally, the thermodynamic stability of 3CLpro H41A, H41D, and C145S variants was reduced relative the wild-type enzyme, with a similar stability of the H41E and C145A variants. Collectively, the above observations confirm the roles of His41 and Cys145 in the catalytic activity and the overall conformational fold of 3CLpro SARS-CoV-2. We conclude that the cysteine-histidine pair should be targeted for inhibition of 3CLpro and development of antiviral against COVID-19 and coronaviruses.In this work, nanosized P-doped SnO2 (SnO2-P) was prepared by a sol-gel method as a catalyst for the V3+/V2+ redox reaction in vanadium redox flow battery. Compared with SnO2, the electrochemical performance of SnO2-P is significantly improved. This is because P doping provides more active sites and shows greatly improved electrical conductivity, thereby increasing the electron transfer rate. As a result, SnO2-P shows better catalytic performance than SnO2. The SnO2-P modified cell is designed, and it exhibits an increase of 47.2 mA h in discharge capacity and 8.7% in energy efficiency compared with the pristine cell at 150 mA cm-2. These increases indicate that the modified cell has a higher electrolyte utilization rate. This study shows that SnO2-P is a new and efficient catalyst for vanadium redox flow battery.Amine acid transformation is an important chemical process in biological systems. As a well-developed and acknowledged tool, chiral aldehyde catalysis provides good catalytic activation and stereoselective control abilities in the asymmetric reaction of N-unprotected amino acid esters and amino acid esters analogs, in which the key to success is the design of the catalysts derived from chiral BINOL aldehyde, which is based on the face control of enolate intermediates. In this review, one of the co-catalytic systems that combined with a transition metal to form a multiplex catalytic system and the well-established multiplex stereocenters of chiral aldehyde catalysis have been reviewed. Finally, a novel organocatalysis is prospected.The ability to radiolabel proteins with [18F]fluoride enables the use of positron emission tomography (PET) for the early detection, staging and diagnosis of disease. The direct fluorination of native proteins through C-F bond formation is, however, a difficult task. The aqueous environments required by proteins severely hampers fluorination yields while the dry, organic solvents that promote nucleophilic fluorination can denature proteins. To circumvent these issues, indirect fluorination methods making use of prosthetic groups that are first fluorinated and then conjugated to a protein have become commonplace. But, when it comes to the radiofluorination of proteins, these indirect methods are not always suited to the short half-life of the fluorine-18 radionuclide (110 min). This review explores radiofluorination through bond formation with fluoride at boron, metal complexes, silicon, phosphorus and sulfur. The potential for these techniques to be used for the direct, aqueous radiolabeling of proteins with [18F]fluoride is discussed.Layered double hydroxides (LDH) are being used as electrocatalysts for oxygen evolution reactions (OERs). However, low current densities limit their practical applications. Herein, we report a facile and economic synthesis of an iron-copper based LDH integrated with a cobalt-based metal-organic framework (ZIF-12) to form LDH-ZIF-12 composite (1) through a co-precipitation method. The as-synthesized composite 1 requires a low overpotential of 337 mV to achieve a catalytic current density of 10 mA cm-2 with a Tafel slope of 89 mV dec-1. Tafel analysis further demonstrates that 1 exhibits a slope of 89 mV dec-1 which is **** lower than the slope of 284 mV dec-1 for LDH and 172 mV dec-1 for ZIF-12. The slope value of 1 is also lower than previously reported electrocatalysts, including Ni-Co LDH (113 mV dec-1) and Zn-Co LDH nanosheets (101 mV dec-1), under similar conditions. Controlled potential electrolysis and stability test experiments show the potential application of 1 as a heterogeneous electrocatalyst for water oxidation.
The nanocarrier with efficient encapsulation ability is potentially applicable for drug delivery, biosensing, biocatalytic, and diagnostic tools.Addressing intracellular targets is a challenging task that requires potent molecular transporters capable to deliver various cargos. Herein, we report the synthesis of hydrophobic macrocycles composed of both amino acids and peptoid monomers. The cyclic tetramers and hexamers were assembled in a modular approach using solid as well as solution phase techniques. To monitor their intracellular localization, the macrocycles were attached to the fluorophore Rhodamine B. Most molecular transporters were efficiently internalized by HeLa cells and revealed a specific accumulation in mitochondria without the need for cationic charges. The data will serve as a starting point for the design of further cyclic peptoid-peptide hybrids presenting a new class of highly efficient, versatile molecular transporters.Coronaviruses are responsible for multiple pandemics and millions of deaths globally, including the current pandemic of coronavirus disease 2019 (COVID-19). Development of antivirals against coronaviruses, including the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) responsible for COVID-19, is essential for containing the current and future coronavirus outbreaks. https://www.selleckchem.com/products/tg003.html SARS-CoV-2 proteases represent important targets for the development of antivirals because of their role in the processing of viral polyproteins. 3-Chymotrypsin-like protease (3CLpro) is one such protease. The cleavage of SARS-CoV-2 polyproteins by 3CLpro is facilitated by a Cys145-His41 catalytic dyad. We here characterized the catalytic roles of the cysteine-histidine pair for improved understanding of the 3CLpro reaction mechanism, to inform the development of more effective antivirals against Sars-CoV-2. The catalytic dyad residues were substituted by site-directed mutagenesis. All substitutions tested (H41A, H41D, H41E, C145A, and C145S) resulted in a complete inactivation of 3CLpro, even when amino acids with a similar catalytic function to that of the original residues were used. The integrity of the structural fold of enzyme variants was investigated by circular dichroism spectroscopy to test if the catalytic inactivation of 3CLpro was caused by gross changes in the enzyme secondary structure. C145A, but not the other substitutions, shifted the oligomeric state of the enzyme from dimeric to a higher oligomeric state. Finally, the thermodynamic stability of 3CLpro H41A, H41D, and C145S variants was reduced relative the wild-type enzyme, with a similar stability of the H41E and C145A variants. Collectively, the above observations confirm the roles of His41 and Cys145 in the catalytic activity and the overall conformational fold of 3CLpro SARS-CoV-2. We conclude that the cysteine-histidine pair should be targeted for inhibition of 3CLpro and development of antiviral against COVID-19 and coronaviruses.In this work, nanosized P-doped SnO2 (SnO2-P) was prepared by a sol-gel method as a catalyst for the V3+/V2+ redox reaction in vanadium redox flow battery. Compared with SnO2, the electrochemical performance of SnO2-P is significantly improved. This is because P doping provides more active sites and shows greatly improved electrical conductivity, thereby increasing the electron transfer rate. As a result, SnO2-P shows better catalytic performance than SnO2. The SnO2-P modified cell is designed, and it exhibits an increase of 47.2 mA h in discharge capacity and 8.7% in energy efficiency compared with the pristine cell at 150 mA cm-2. These increases indicate that the modified cell has a higher electrolyte utilization rate. This study shows that SnO2-P is a new and efficient catalyst for vanadium redox flow battery.Amine acid transformation is an important chemical process in biological systems. As a well-developed and acknowledged tool, chiral aldehyde catalysis provides good catalytic activation and stereoselective control abilities in the asymmetric reaction of N-unprotected amino acid esters and amino acid esters analogs, in which the key to success is the design of the catalysts derived from chiral BINOL aldehyde, which is based on the face control of enolate intermediates. In this review, one of the co-catalytic systems that combined with a transition metal to form a multiplex catalytic system and the well-established multiplex stereocenters of chiral aldehyde catalysis have been reviewed. Finally, a novel organocatalysis is prospected.The ability to radiolabel proteins with [18F]fluoride enables the use of positron emission tomography (PET) for the early detection, staging and diagnosis of disease. The direct fluorination of native proteins through C-F bond formation is, however, a difficult task. The aqueous environments required by proteins severely hampers fluorination yields while the dry, organic solvents that promote nucleophilic fluorination can denature proteins. To circumvent these issues, indirect fluorination methods making use of prosthetic groups that are first fluorinated and then conjugated to a protein have become commonplace. But, when it comes to the radiofluorination of proteins, these indirect methods are not always suited to the short half-life of the fluorine-18 radionuclide (110 min). This review explores radiofluorination through bond formation with fluoride at boron, metal complexes, silicon, phosphorus and sulfur. The potential for these techniques to be used for the direct, aqueous radiolabeling of proteins with [18F]fluoride is discussed.Layered double hydroxides (LDH) are being used as electrocatalysts for oxygen evolution reactions (OERs). However, low current densities limit their practical applications. Herein, we report a facile and economic synthesis of an iron-copper based LDH integrated with a cobalt-based metal-organic framework (ZIF-12) to form LDH-ZIF-12 composite (1) through a co-precipitation method. The as-synthesized composite 1 requires a low overpotential of 337 mV to achieve a catalytic current density of 10 mA cm-2 with a Tafel slope of 89 mV dec-1. Tafel analysis further demonstrates that 1 exhibits a slope of 89 mV dec-1 which is much lower than the slope of 284 mV dec-1 for LDH and 172 mV dec-1 for ZIF-12. The slope value of 1 is also lower than previously reported electrocatalysts, including Ni-Co LDH (113 mV dec-1) and Zn-Co LDH nanosheets (101 mV dec-1), under similar conditions. Controlled potential electrolysis and stability test experiments show the potential application of 1 as a heterogeneous electrocatalyst for water oxidation.
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