基礎講座 電気泳動(Electrophoresis)

/pdf/thrombosis-and-haemostasis-210r9dge9h.pdf

Thrombosis and haemostasis.

the malarial parasite is the invasion of the host red blood cell by the merozoite form of the parasite which leads to its multiplication within the erythrocyte and the eventual rup- ture of the cell and release of daughter merozoites. 'Malaria and the Red Cell' was the subject of a recent Ciba Foundation Symposium *. Electron microscopy has shown that a complex sequence of events occurs during invasion of the erythrocyte ~. After initial recognition and attachment, a junction is formed between the merozoite and erythro- cyte and the area of host membrane around this junction progressively invaginates around the parasite until it seals off and totally encloses the parasite within the cytoplasm of the erythrocyte. Malarial parasites show considerable host specificity which depends, at least in part, on specific recognition between the merozoite and the red cell surface during the early events in this process. In the case of the human malarias, the erythrocyte Duffy antigens are probably involved in invasion by Plasmodiurn vivax but not P. falciparurn 2,3. The recent progress in defining the human erythrocyte receptors for P. falciparum was discussed by G. Pasvol (University of Oxford), who presented results which suggest that two different regions of the major erythrocyte membrane sialoglycoprotein a (glycopho- rin A) are involved in invasion by this para- site. He has shown that the extent of in- vasion correlates with the amount of sialo- glycoprotein o~ in the cells. Erythrocyte variants deficient in this sialoglycoprotein are relatively resistant to invasion 4 and the invasion of nucleated erythroid precursor cells of different maturity parallels the

Trends in Biochemical Sciences

Hematology/Oncology Clinics of North America

Thermophoresis for characterizing biomolecular interaction.

Gold complexes with N-heterocyclic carbene (NHC) ligands have been attracting major attention in medicinal inorganic chemistry based on their favorable antiproliferative effects and the structural versatility of the coordinated NHC ligands. Here we present a novel complex of the type (NHC)2Au+, which represents a substantially improved and selective TrxR inhibitor compared to close structural analogues. The complex is highly stable in various solutions over 96 hours, however, comparative cellular uptake studies indicate metabolic transformations inside cells over time. A portfolio of other gold complexes (e.g. Auranofin) has been used as references in key biological assays, showing that the novel (NHC)2Au+ complex exhibits substantially lower protein binding in combination with a strongly enhanced cytotoxic activity.

A gold(I) biscarbene complex with improved activity as a TrxR inhibitor and cytotoxic drug: comparative studies with different gold metallodrugs

The prediction of protein–ligand interactions and their corresponding binding free energy is a challenging task in structure-based drug design and related applications. Docking and scoring is broadly used to propose the binding mode and underlying interactions as well as to provide a measure for ligand affinity or differentiate between active and inactive ligands. Various studies have revealed that most docking software packages reliably predict the binding mode, although scoring remains a challenge. Here, a diverse benchmark data set of 99 matched molecular pairs (3D-MMPs) with experimentally determined X-ray structures and corresponding binding affinities is introduced. This data set was used to study the predictive power of 13 commonly used scoring functions to demonstrate the applicability of the 3D-MMP data set as a valuable tool for benchmarking scoring functions.

https://pubs.acs.org/doi/pdf/10.1021/acsomega.7b01194

A Diverse Benchmark Based on 3D Matched Molecular Pairs for Validating Scoring Functions.

A fast and precise affinity capillary electrophoresis (ACE) method has been developed and applied for the investigation of the binding interactions between P-selectin and heparinoids as potential P-selectin inhibitors in the presence and absence of calcium ions. Furthermore, model proteins and vitronectin were used to appraise the binding behavior of P-selectin. The normalized mobility ratios (∆R/Rf ), which provided information about the binding strength and the overall charge of the protein-ligand complex, were used to evaluate the binding affinities. It was found that P-selectin interacts more strongly with heparinoids in the presence of calcium ions. P-selectin was affected by heparinoids at the concentration of 3 mg/L. In addition, the results of the ACE experiments showed that among other investigated proteins, albumins and vitronectin exhibited strong interactions with heparinoids. Especially with P-selectin and vitronectin, the interaction may additionally induce conformational changes. Subsequently, computational models were applied to interpret the ACE experiments. Docking experiments explained that the binding of heparinoids on P-selectin is promoted by calcium ions. These docking models proved to be particularly well suited to investigate the interaction of charged compounds, and are therefore complementary to ACE experiments.

Shantheya Balasupramaniam

Papers

A gold(I) biscarbene complex with improved activity as a TrxR inhibitor and cytotoxic drug: comparative studies with different gold metallodrugs

A Diverse Benchmark Based on 3D Matched Molecular Pairs for Validating Scoring Functions.

Using affinity capillary electrophoresis and computational models for binding studies of heparinoids with p‐selectin and other proteins