3/18/2023 0 Comments Rosetta stone totale error 2124![]() ![]() ![]() There are currently no vaccines or antiviral therapeutics to treat HPIV3 or RSV infections. Human parainfluenza virus 3 (HPIV3) and respiratory syncytial virus (RSV) are leading causes of lower respiratory tract infections. We experimentally observed the hydrogen-bond mediated J-couplings between Nδ1 and Nε2 of adjacent His37 imidazole rings, providing direct evidence for the existence of various imidazolium-imidazole hydrogen-bonding geometries in the histidine tetrad at low pH, thus validating the proton conduction mechanism in the M2FL protein by which the proton is transferred through the breaking and reforming of the hydrogen bonds between pairs of His37 residues. Here, we report on the measurement of 15N–15N J-couplings of 15N His37-labeled full length M2 (M2FL) protein from Influenza A virus embedded in synthetic liquid crystalline lipid bilayers using two-dimensional J-resolved NMR spectroscopy. However, the hydrogen bonding partnership remains unresolved. The proton conductance mechanism has been extensively debated in the literature, but it is accepted that the proton conductance is facilitated by hydrogen bonds involving the His37 residues. The integral membrane M2 protein is a 97-residue membrane protein that assembles as a tetramer to conduct protons at a slow rate (102–103/s) when activated by low pH. Single molecule force spectroscopy (SMFS) reveals that the force necessary to activate the CB molecular gate on the time scale of 100 ms is approximately 2 nN. Experimental and computational evidence further indicate that the ungated ketal possesses mechanical strength that is commensurate with the conventional polymer backbones. The sequential treatment of ultrasonication followed by acid, however, leads to a further 11-fold decrease in molecular weight to 2.5 kDa. In the presence of an acid trigger alone, the pristine polymer retains its backbone integrity, and delivering high mechanical forces alone by ultrasonication degrades the polymer to an apparent limiting molecular weight of 28 kDa. ![]() This gated ketal is further incorporated into the polymer backbone. A cyclobutane (CB) mechanophore is used as a mechanical gate to regulate an acid-sensitive ketal that has been widely employed in acid degradable polymers. Herein, we report a strategy that combats unintended degradation in polymers by combining two common degradation stimuli-mechanical and acid triggers-in an “AND gate” fashion. The rare combination of two intrinsically conflicting properties, i.e., backbone stability and accessible degradability, can make this polymer a potential option for new sustainable materials.ĭegradable polymers are desirable for the replacement of conventional organic polymers that persist in the environment, but they often suffer from the unintentional scission of the degradable functionalities on the polymer backbone, which diminishes polymer properties during storage and regular use. When backbone degradation is needed, the degradability can be unlocked by mechanochemical activation that converts the pol圜BL into a linear polyester. The cyclobutane keeps polymer backbone intact under conditions that hydrolyze the lactone and allows the ester group to be recovered when undesirable hydrolysis occurs. ![]() This strategy is demonstrated with a cyclobutane-fused lactone (CBL) polymer. Here we report a general strategy to overcome this issue: “locking” the degradability during handling and use of the polymers and “unlocking” it when degradation is needed. Particularly, the degradability of a conventional degradable polymer is typically enabled by cleavable groups on the backbone, which can be attacked by stimuli in ambient conditions, causing undesirable material deterioration. Though numerous applications require degradable polymers, there are surprisingly few polymer systems that combine superior stability and controllable degradability. ![]()
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