Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment

Intracellular antibodies can inhibit disease-relevant protein interactions, but inefficient cellular uptake limits their utility. Using a RAS-targeting intracellular antibody as a screening tool, the authors here identify small molecules that inhibit RAS-effector interactions and readily penetrate cells

Design and synthesis of Quinazolinone-based libraries for inhibitation of Kinase activity and hit-to-lead optimisation of Wnt pathway inhibitors

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Editorial : Competence in scientific agriculture

<div><p>Human arylamine <i>N</i>-acetyltransferase 1 (hNAT1) has become an attractive potential biomarker for estrogen-receptor-positive breast cancers. We describe here the mechanism of action of a selective non-covalent colorimetric biosensor for the recognition of hNAT1 and its murine homologue, mNat2, over their respective isoenzymes, leading to new opportunities in diagnosis. On interaction with the enzyme, the naphthoquinone probe undergoes an instantaneous and striking visible color change from red to blue. Spectroscopic, chemical, molecular modelling and biochemical studies reported here show that the color change is mediated by selective recognition between the conjugate base of the sulfonamide group within the probe and the conjugate acid of the arginine residue within the active site of both hNAT1 and mNat2. This represents a new mechanism for selective biomarker sensing and may be exploited as a general approach to the specific detection of biomarkers in disease.</p></div

Inhibitor binding pocket of hNAT1 and mNat2.

<p>(<b>a</b>) The active site of hNAT1 crystal structure (PDB:2PQT) in surface representation with <b>1</b> docked in stick representation. The hNAT1 residues involved in inhibitor binding and selectivity are shown in stick representation and labeled with carbon in green, nitrogen in blue, oxygen in red, and sulfur in yellow. <b>1</b> is labeled with carbon atoms in light orange, nitrogen in blue, oxygen in red, and sulfur in yellow. (<b>b</b>) The active site of mNat2 structural model with docked compound <b>1</b> is shown using the same representation as in (a).</p

Competitive inhibition of 1 towards mNat2 and active site differences in mammalian NATs

<p>(<b>a</b>) <b>Left panel</b>: Structure of compound <b>1</b>; <b>Right panel</b>: Dixon plot shows competitive inhibition of mNat2 (9 ng) by <b>1</b> at different pABA concentrations (25 µM (circles), 50 µM (triangles), 100 µM (diamonds), and 250 µM (squares)). Initial rates of the mNat2 catalysed reaction were determined by monitoring the rate of hydrolysis of AcCoA (400 μM) (<b>b</b>) Summary table of active site differences of human and murine NATs and the effects of their interaction with <b>1</b>. Blue and red columns indicate the color of <b>1</b> on interaction with the protein.</p

Advances in Science No. 01

Esta publicación tiene la decidida intención de acercar la investigación que realiza la Universidad del Rosario de Bogotá, Colombia, a un gran número de lectores para mostrarles, desde el periodismo científico, el quehacer investigativo de la institución. Queremos presentarle al mundo, tal como lo dijo hace dos siglos uno de nuestros hijos más ilustres, Francisco José de Caldas, el sentido final del ejercicio de investigar: “[...] todo para bienestar de los hombres”.It is the explicit goal of this publication is to get research carried out by the Universidad del Rosario in Bogotá, Colombia to a large number of readers, showing them, through sci-ence journalism, the daily investigative work carried out at this institution. And we want the world to see it in the spirit of the ultimate meaning of the practice of research, just as it was expressed two centuries ago by one of our most illustrious sons, Francisco José de Caldas, who underlined that it is “all for the well-being of humankind.

XX Semana de la Enseñanza de la Física

25 a 29 de septiembre de 2017Facultad de Ciencias y EducaciónProyecto Curricular de Licenciatura en FísicaUniversidad Distrital Francisco José de Calda