First-in-Human Phase 1 Study To Assess Safety, Tolerability, and Pharmacokinetics of a Novel Antifungal Drug, VL-2397, in Healthy Adults.

VL-2397 is an antifungal drug with a novel mechanism of action, rapid fungicidal activity, and potent activity against , including azole-resistant strains. VL2397-101, a phase 1 first-in-human, randomized, double-blind, placebo-controlled dose-escalation study, was conducted in healthy adults to determine the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous (i.v.

Phase 1 clinical trials of the safety and immunogenicity of adjuvanted plasmid DNA vaccines encoding influenza A virus H5 hemagglutinin.

Background: Development of vaccines against highly pathogenic avian influenza virus H5N1 subtypes posing a pandemic threat remains a priority. Limitations in manufacturing capacity and production time of conventional inactivated vaccines highlight the need for additional approaches.

Methods: We conducted two double-blind, placebo-controlled phase 1 studies involving a total of 103 healthy adults who received two intramuscular injections of Vaxfectin-adjuvanted plasmid DNA vaccine or placebo 21 days apart.

CuZn Superoxide Dismutase Geometry Optimization, Energetics, and Redox Potential Calculations by Density Functional and Electrostatic Methods.

The structures, energetics, and orbital- and charge-dependent properties of copper zinc superoxide dismutase (CuZnSOD) have been studied using density functional and electrostatic methods. The CuZnSOD was represented with a model consisting of copper and zinc sites connected by a bridging histidine ligand. In addition to the bridge, three histidine ligands and one water molecule were bonded to the Cu ion in the copper site as first-shell ligands.

Density Functional and Electrostatic Calculations of Manganese Superoxide Dismutase Active Site Complexes in Protein Environments.

Density functional and electrostatic methods have been applied to calculate active site geometries and the redox potential of manganese superoxide dismutase (MnSOD). The initial active site clusters were built up by including only first-shell side chain ligands and then augmented by second-shell ligands. The density functional optimized Mn-ligand bond lengths for the reduced complexes in general compared fairly well with protein crystallography data; however, large deviations for calculated Mn-OH distances were found for the oxidized active site clusters.