A combined modeling approach was used to identify structural factors that underlie the structure-activity relationships (SARs) of full dopamine D₂ receptor agonists and structurally similar inactive compounds. A 3D structural model of the dopamine D₂ receptor was constructed, with the agonist (-)-(R)-2-OH-NPA present in the binding site during the modeling procedure. The 3D model was evaluated ...

A pharmacophore-based approach for compiling focused screening libraries is presented. It integrates information from three-dimensional molecular alignments into correlation vector-based database screening. The pharmacophore model is represented by a number of spheres of Gaussian-distributed feature densities. Different degrees of "fuzziness" can be introduced to influence the model's resolutio...

Three dimensional pharmacophore models can be considered as an ensemble of steric and electronic features in space, which are necessary to ensure intermolecular interaction with a specific target in order to trigger or to block biological activity [1]. By identifying these features, a 3D pharmacophore model can be built in order to screen multi-conformatorial databases with the aim to detect co...

The photoaffinity analog 2-azido-AMP was found to be a potent allosteric inhibitor of pig kidney fructose 1,6-bisphosphatase. UV-induced covalent incorporation of 2-azido-[8-3H]AMP fully inactivated the enzyme at a level stoichiometric with its subunit composition (4 mol of analog/mol of tetramer). The photoincorporation and inactivation were prevented by the presence of AMP but not by the subs...

Based on a literature precedent, preparation of methyl 4-azido-3,4,6-trideoxy-3-fluoro-alpha-D-mannopyranoside (18) was attempted via fluorination of methyl 4-azido-2-O-benzyl-4,6-dideoxy-alpha-D-altropyranoside with diethylaminosulfur trifluoride (DAST). Contrary to expectations, the reaction took place with retention of configuration at the site of the fluorination yielding methyl 4-azido-2-O...

Castanospermine and 3'-azido-3'-deoxythymidine (zidovudine) were evaluated in combination against human immunodeficiency virus (HIV) replication in vitro. Castanospermine and 3'-azido-3'-deoxythymidine inhibited HIV type 1 synergistically in acutely infected H9 cells. In addition, they synergistically inhibited both HIV type 1 and HIV type 2 in peripheral blood mononuclear cells. There were no ...

An azido-avermectin analog [4'' alpha-(4-azidosalicylamido-epsilon-caproylamido-beta-alan ylamido)-4''-deoxyavermectin B1a; azido-AVM] was synthesized and used to photoaffinity label avermectin binding sites present in the membranes of Caenorhabditis elegans and Drosophila melanogaster. Azido-AVM was biologically active and behaved like a competitive inhibitor of [3H]ivermectin binding to C. el...

An analog of ADP containing an azido group at the C-2 position of the purine ring has been synthesized and used as an affinity probe of the membrane-bound coupling factor 1 of spinach chloroplast thylakoid membranes. The 2-azido-ADP inhibited light-induced dark binding of ADP at the tight nucleotide binding site on the thylakoid membranes. The 2-azido-ADP itself bound tightly to the thylakoid m...

Disulfide- and terminal alkyne-modified magnetic silica particles (DA-MSPs) were synthesized and used to covalently capture and reductively release azido glycopeptides via click chemistry and dithiothreitol treatment. Using DA-MSPs, an efficient and specific enrichment method for separating azido glycopeptides has been developed.