47 research outputs found

    Editorial:Spotlight on Japan - chemical sciences 2023

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    Generation of novel cationic antimicrobial peptides from natural non-antimicrobial sequences by acid-amide substitution

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    <p>Abstract</p> <p>Background</p> <p>Cationic antimicrobial peptides (CAMPs) are well recognized to be promising as novel antimicrobial and antitumor agents. To obtain novel skeletons of CAMPs, we propose a simple strategy using acid-amide substitution (i.e. Glu→Gln, Asp→Asn) to confer net positive charge to natural non-antimicrobial sequences that have structures distinct from known CAMPs. The potential of this strategy was verified by a trial study.</p> <p>Methods</p> <p>The pro-regions of nematode cecropin P1-P3 (P1P-P3P) were selected as parent sequences. P1P-P3P and their acid-amide-substituted mutants (NP1P-NP3P) were chemically synthesized. Bactericidal and membrane-disruptive activities of these peptides were evaluated. Conformational changes were estimated from far-ultraviolet circular dichroism (CD) spectra.</p> <p>Results</p> <p>NP1P-NP3P acquired potent bactericidal activities via membrane-disruption although P1P-P3P were not antimicrobial. Far-ultraviolet CD spectra of NP1P-NP3P were similar to those of their parent peptides P1P-P3P, suggesting that NP1P-NP3P acquire microbicidal activity without remarkable conformational changes. NP1P-NP3P killed bacteria in almost parallel fashion with their membrane-disruptive activities, suggesting that the mode of action of those peptides was membrane-disruption. Interestingly, membrane-disruptive activity of NP1P-NP3P were highly diversified against acidic liposomes, indicating that the acid-amide-substituted nematode cecropin pro-region was expected to be a unique and promising skeleton for novel synthetic CAMPs with diversified membrane-discriminative properties.</p> <p>Conclusions</p> <p>The acid-amide substitution successfully generated some novel CAMPs in our trial study. These novel CAMPs were derived from natural non-antimicrobial sequences, and their sequences were completely distinct from any categories of known CAMPs, suggesting that such mutated natural sequences could be a promising source of novel skeletons of CAMPs.</p

    Factors determining maximum torque and achievement of the recommended torque for manual implant drivers: A pilot study

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    When fixing an oral implant superstructure with a screw, operators must be aware of the torque being applied by their fingers to prevent the transmission of excessive or insufficient torque to the implant. In this study, we identified the factors that determine individual maximum attainable torque and those that determine the achievement of the prescribed torque. We evaluated 16 dentists on their use of two types of manual implant drivers(UniGrip by Nobel Biocare and Carrier Hex by Zimmer Biomet)and measured the maximum torque(MT)generated by their fingers. The target torque was set at 15N. Measurements were taken while the participants were turning the implant screw with or without gloves in both clockwise and counterclockwise directions. The grip and finger strength of each participant were measured, and the data showed that torque values were higher among the male participants during clockwise rotation and when they were wearing gloves(p<0.05). Positive correlations were found between the MT and grip strength and between the MT and finger strength. These results suggest that dentists should monitor their ability to consistently achieve the recommended torque for implant drivers

    4-Methoxybenzyloxymethyl Group, a Racemization-Resistant Protecting Group for Cysteine in Fmoc Solid Phase Peptide Synthesis

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    The 4-methoxybenzyloxymethyl (MBom) group was introduced for sulfhydryl protection of Cys in combination with Fmoc chemistry. The MBom group proved to substantially suppress racemization of Cys during its incorporation mediated by phosphonium or uronium reagents. Furthermore, this group was found to significantly reduce racemization of the C-terminal Cys linked to a hydroxyl resin during repetitive base treatment, in comparison with the usually used trityl (Trt) and acetamidomethyl (Acm) groups

    Postsynthetic Modification of Unprotected Peptides via <i>S</i>‑Tritylation Reaction

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    Tritylation using trityl alcohol (Trt–OH) in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) is a convenient and efficient procedure that can offer <i>S</i>-protection of the Cys located in fully unprotected peptides. The procedure simply requires Trt–OH and HFIP to selectively promote <i>S</i>-tritylation in the presence of peptide nucleophilic functionalities

    Synthesis of Cysteine-Rich Peptides by Native Chemical Ligation without Use of Exogenous Thiols

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    Native chemical ligation (NCL) performed without resorting to the use of thiol additives was demonstrated to be an efficient and effective procedure for synthesizing Cys-rich peptides. This method using tris­(2-carboxyethyl)­phosphine (TCEP) as a reducing agent facilitates the ligation reaction even at the Thr-Cys or Ile-Cys site and enables one-pot synthesis of Cys-rich peptides throughout NCL and oxidative folding
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