Tetrazole as a Replacement of the Electrophilic Group in Characteristic Prolyl Oligopeptidase Inhibitors

4-Phenylbutanoyl-aminoacyl-2(S)-tetrazolylpyrrolidines were studied as prolyl oligopeptidase inhibitors. The compounds were more potent than expected from the assumption that the tetrazole would also here be a bioisostere of the carboxylic acid group and the corresponding carboxylic acids are at their best only weak inhibitors. The aminoacyl groups L-prolyl and L-alanyl gave potent inhibitors with IC50 values of 12 and 129 nM, respectively. This was in line with typical prolyl oligopeptidase inhibitors; however, we did observe a difference with N-methyl-L-alanyl, which gave potent inhibitors in typical prolyl oligopeptidase inhibitors but not in our novel compound series. Furthermore, all studied 4-phenylbutanoyl-aminoacyl-2(S)-tetrazolylpyrrolidines decreased alpha-synuclein dimerization at the concentration of 10 mu M, also when they were only weak inhibitors of the proteolytic activity of the enzyme with an IC50 value of 205 mu M. Molecular docking studies revealed that the compounds are likely to bind differently to the enzyme compared to typical prolyl oligopeptidase inhibitors represented in this study by 4-phenylbutanoyl-aminoacyl-2(S)-cyanopyrrolidines.Peer reviewe

2-Imidazole as a Substitute for the Electrophilic Group Gives Highly Potent Prolyl Oligopeptidase Inhibitors

Different five-membered nitrogen-containing heteroaromatics in the position of the typical electrophilic group in prolyl oligopeptidase (PREP) inhibitors were investigated and compared to tetrazole. The 2-imidazoles were highly potent inhibitors of the proteolytic activity. The binding mode for the basic imidazole was studied by molecular docking as it was expected to differ from the acidic tetrazole. A new putative noncovalent binding mode with an interaction to His680 was found for the 2-imidazoles. Inhibition of the proteolytic activity did not correlate with the modulating effect on protein-protein-interaction-derived functions of PREP (i.e., dimerization of alpha-synuclein and autophagy). Among the highly potent PREP inhibiting 2-imidazoles, only one was also a potent modulator of PREP-catalyzed alpha-synuclein dimerization, indicating that the linker length on the opposite side of the molecule from the five-membered heteroaromatic is critical for the disconnected structure-activity relationships

Pedagogical approaches for e-assessment with authentication and authorship verification in Higher Education

Checking the identity of students and authorship of their online submissions is a major concern in Higher Education due to the increasing amount of plagiarism and cheating using the Internet. The literature on the effects of e-authentication systems for teaching staff is very limited because it is a novel procedure for them. A considerable gap is to understand teaching staff’ views regarding the use of e-authentication instruments and how they impact trust in e-assessment. This mixed-method study examines the concerns and practices of 108 teaching staff who used the TeSLA - Adaptive Trust-based e-Assessment System in six countries: UK, Spain, Netherlands, Bulgaria, Finland and Turkey. The findings revealed some technological, organisational and pedagogical issues related to accessibility, security, privacy and e-assessment design and feedback. Recommendations are to provide: a FAQ and an audit report with results, to raise awareness about data security and privacy, to develop policies and guidelines about fraud detection and prevention, e-assessment best practices and course team support

Automatic student plagiarism detection : future perspectives

The availability and use of computers in teaching has seen an increase in the rate of plagiarism among students because of the wide availability of electronic texts online. While computer tools that have appeared in the recent years are capable of detecting simple forms of plagiarism, such as copy-paste, a number of recent research studies devoted to evaluation and comparison of plagiarism detection tools revealed that these contain limitations in detecting complex forms of plagiarism such as extensive paraphrasing and use of technical tricks, such as replacing original characters with similar-looking characters from foreign alphabets. This article investigates limitations in automatic detection of student plagiarism and proposes ways on how these issues could be tackled in future systems by applying various natural language processing and information retrieval technologies. A classification of types of plagiarism is presented, and an analysis is provided of the most promising technologies that have the potential of dealing with the limitations of current state-of-the-art systems. Furthermore, the article concludes with a discussion on legal and ethical issues related to the use of plagiarism detection software. The article, hence, provides a "roadmap" for developing the next generation of plagiarism detection systems

2-Imidazole as a Substitute for the Electrophilic Group Gives Highly Potent Prolyl Oligopeptidase Inhibitors

Different five-membered nitrogen-containing heteroaromatics in the position of the typical electrophilic group in prolyl oligopeptidase (PREP) inhibitors were investigated and compared to tetrazole. The 2-imidazoles were highly potent inhibitors of the proteolytic activity. The binding mode for the basic imidazole was studied by molecular docking as it was expected to differ from the acidic tetrazole. A new putative noncovalent binding mode with an interaction to His680 was found for the 2-imidazoles. Inhibition of the proteolytic activity did not correlate with the modulating effect on protein-protein-interaction-derived functions of PREP (i.e., dimerization of alpha-synuclein and autophagy). Among the highly potent PREP inhibiting 2-imidazoles, only one was also a potent modulator of PREP-catalyzed alpha-synuclein dimerization, indicating that the linker length on the opposite side of the molecule from the five-membered heteroaromatic is critical for the disconnected structure-activity relationships.Peer reviewe