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1.
Chimia (Aarau) ; 77(10): 679-682, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-38047865

RESUMO

Many students assume a molecular structure for all substances, even after being instructed on the topic. But why do students struggle to understand key concepts like chemical bonding? One of the reasons is students' tendency to overgeneralize: Students wrongfully transfer characteristics from familiar (e.g., molecular substances) to lesser-known concepts (e.g., ionic compounds). In this article, possible reasons behind this commonly observed tendency are discussed and a possible didactical solution is proposed. Comparing and contrasting approaches increased students' ability to distinguish between similar concepts in mathematics.[1] The method of comparing and contrasting is therefore applied by simultaneously introducing the three types of chemical bonding to effectively tackle students' overgeneralization tendencies.

2.
Chemistry ; 23(36): 8585-8589, 2017 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-28513883

RESUMO

Tris(2-carboxyethyl)phosphine (TCEP) is an often-used reducing agent in biochemistry owing to its selectivity towards disulfide bonds. As TCEP causes undesired consecutive side reactions in various analytical methods (e.g., gel electrophoresis, protein labeling), it is usually removed by means of dialysis or gel filtration. Here, an alternative method of separation is presented, namely the immobilization of TCEP on magnetic nanoparticles. This magnetic reagent provides a simple and rapid approach to remove the reducing agent after successful reduction. A reduction capacity of 70 µmol per gram of particles was achieved by using surface-initiated atom transfer polymerization.

3.
J Med Chem ; 60(12): 4840-4860, 2017 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-28537728

RESUMO

Target-based approaches toward new antimalarial treatments are highly valuable to prevent resistance development. We report several series of pyrazolopyran-based inhibitors targeting the enzyme serine hydroxymethyltransferase (SHMT), designed to improve microsomal metabolic stability and to identify suitable candidates for in vivo efficacy evaluation. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target assays and PfNF54 strains in cell-based assays with values in the low nanomolar range (3.2-55 nM). A set of carboxylate derivatives demonstrated markedly improved in vitro metabolic stability (t1/2 > 2 h). A selected ligand showed significant in vivo efficacy with 73% of parasitemia reduction in a mouse model. Five new cocrystal structures with PvSHMT were solved at 2.3-2.6 Å resolution, revealing a unique water-mediated interaction with Tyr63 at the end of the para-aminobenzoate channel. They also displayed the high degree of conformational flexibility of the Cys364-loop lining this channel.


Assuntos
Antimaláricos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Glicina Hidroximetiltransferase/antagonistas & inibidores , Animais , Antimaláricos/química , Proteínas de Arabidopsis/antagonistas & inibidores , Técnicas de Química Sintética , Cristalografia por Raios X , Cisteína/química , Estabilidade de Medicamentos , Inibidores Enzimáticos/metabolismo , Glicina Hidroximetiltransferase/metabolismo , Meia-Vida , Ligantes , Malária Falciparum/tratamento farmacológico , Camundongos SCID , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/enzimologia , Plasmodium falciparum/patogenicidade , Plasmodium vivax/enzimologia , Conformação Proteica , Ratos , Relação Estrutura-Atividade , Tiofenos/síntese química , Tiofenos/farmacologia
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