Recent advances in proteasome inhibitor discovery.

INTRODUCTION: Proteasome inhibition is a quickly advancing subject of research and has a significant potential to become a potent therapeutic modality for many diseases and disorders. The aim of this review is to present the reader with the variety of approaches to the proteasome inhibitor discovery as well as highlight the diversity of scaffolds being considered for this task. AREAS COVERED: This review focuses on current developments in proteasome inhibitor discovery, including an account of research efforts covered in the literature from the years 2009 - 2012, although some of the earlier work is also mentioned. Specifically, presented are the type of experiments performed, the compounds and compound families investigated along with their activities and assessment for potential therapeutic value. In particular, authors highlight different paths to discovery of the proteasome inhibitors such as screening of large libraries, repurposing of existing therapeutics, development of compounds with known proteasome inhibitory activities as well as utilizing novel scaffolds. EXPERT OPINION: Discovery of therapeutically successful proteasome inhibitors depends on a number of factors and demands a multipronged approach. Screening protocols, choice of assays, desired mode of action, selection of a binding pocket, targeting and delivery strategy, all require careful consideration when attempting to target the proteasome.

Design and development of an automated flow injection instrument for the determination of arsenic species in natural waters.

The design and development of an automated flow injection instrument for the determination of arsenite [As(III)] and arsenate [As(V)] in natural waters is described. The instrument incorporates solenoid activated self-priming micropumps and electronic switching valves for controlling the fluidics of the system and a miniature charge-coupled device spectrometer operating in a graphical programming environment. The limits of detection were found to be 0.79 and 0.98 microM for As(III) and As(V), respectively, with linear range of 1-50 microM. Spiked ultrapure water samples were analyzed and recoveries were found to be 97%-101% for As(III) and 95%-99% for As(V), respectively. Future directions in terms of automation, optimization, and field deployment are discussed.