Azodicarbonamide inhibits HIV-1 replication by targeting the nucleocapsid protein.

Nucleocapsid p7 (NCp7) proteins of human immunodeficiency virus type 1 (HIV-1) contain two zinc binding domains of the sequence Cys-(X)2-Cys-(X)4-His-(X)4-Cys (CCHC). The spacing pattern and metal-chelating residues (3 Cys, 1 His) of these nucleocapside CCHC zinc fingers are highly conserved among retroviruses. These CCHC domains are required during both the early and late phases of retroviral replication, making them attractive targets for antiviral agents. toward that end, we have identified a number of antiviral chemotypes that electrophilically attack the sulfur atoms of the zinc-coordinating cysteine residues of the domains. Such nucleocapside inhibitors were directly virucidal by preventing the initiation of reverse transcription and blocked formation of infectious virus from cells through modification of CCHC domains within Gag precursors. Herein we report that azodicarbonamide (ADA) represents a new compound that inhibits HIV-1 and a broad range of retroviruses by targeting the the nucleocapsid CCHC domains. Vandevelde et al. also recently disclosed that ADA inhibits HIV-1 infection via an unidentified mechanism and that ADA was introduced into Phase I/II clinical trials in Europe for advanced AIDS. These studies distinguish ADA as the first known nucleocapsid inhibitor to progress to human trials and provide a lead compound for drug optimization.

Manganese oxide octahedral molecular sieves: preparation, characterization, and applications.

A thermally stable 3 x 3 octahedral molecular sieve corresponding to natural todorokite (OMS-1) has been synthesized by autoclaving layer-structure manganese oxides, which are prepared by reactions of MnO(4)(-) and Mn(2+) under markedly alkaline conditions. The nature and thermal stability of products depend strongly on preparation parameters, such as the MnO(4)(-)/Mn(2+) ratio, pH, aging, and autoclave conditions. The purest and the most thermally stable todorokite is obtained at a ratio of 0.30 to 0.40. Autoclave treatments at about 150 degrees to 180 degrees C for more than 2 days yield OMS-1, which is as thermally stable (500 degrees C) as natural todorokite minerals. Adsorption data give a tunnel size of 6.9 angstroms and an increase of cyclohexane or carbon tetrachloride uptake with dehydration temperature up to 500 degrees C. At 600 degrees C, the tunnel structure collapses. Both Lewis and Brönsted acid sites have been observed in OMS-1. Particular applications of these materials include adsorption, electrochemical sensors, and oxidation catalysis.