Designing New Protoporphyrinogen Oxidase-Inhibitors Carrying Potential Side Chain Isosteres to Enhance Crop Safety and Spectrum of Activity.

There are several methods to control weeds, which impose particular challenges for farmers in all parts of the world, although applying small molecular compounds still remains the most efficient technology to date. However, plants can evolve to become resistant toward active ingredients which is also the case for protoporphyrinogen oxidase (PPO) inhibitors, a class of highly effective herbicides in use for more than 50 years. Hence, it is essential to continuously discover and develop new herbicidal PPO inhibitors with enhanced intrinsic activity, an improved resistance profile, enhanced crop safety, favorable physicochemical properties, and a clean toxicological profile.

Design, synthesis and screening of herbicidal activity for new phenyl pyrazole-based protoporphyrinogen oxidase-inhibitors (PPO) overcoming resistance issues.

Background: Whilst there are several methods to control weeds, which continuously plague farmers around the globe, the application of small molecular compounds is still the most effective technology to date. Plants can evolve to become resistant to PPO-inhibitors, a class of herbicides in commercial use since the 1960s. It is therefore essential to continuously develop new herbicides based on this mode-of-action with enhanced intrinsic activity, an improved resistance profile and favourable physicochemical properties.

Judicial expertise in the post-pandemic era.

Introduction: In December 2019, the new coronavirus was recognized as the etiologic agent of a severe case of pneumonia in the city of Wuhan, China. The COVID-19 outbreak was initially defined by a series of epicenters and arrived in Brazil in February 2020, causing social isolation and suspension of on-site service provision, including in the Judiciary. There has been an exponential increase in lawsuits awaiting judicial expertise.

First crystal structures of 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) from Mycobacterium tuberculosis indicate a distinct mechanism of intermediate stabilization.

The development of drug resistance by Mycobacterium tuberculosis and other pathogenic bacteria emphasizes the need for new antibiotics. Unlike animals, most bacteria synthesize isoprenoid precursors through the MEP pathway. 1-Deoxy-D-xylulose 5-phosphate synthase (DXPS) catalyzes the first reaction of the MEP pathway and is an attractive target for the development of new antibiotics.

Identification of a 1-deoxy-D-xylulose-5-phosphate synthase (DXS) mutant with improved crystallographic properties.

In this report, we describe a truncated Deinococcus radiodurans 1-deoxy-D-xylulose-5-phosphate synthase (DXS) protein that retains enzymatic activity, while slowing protein degradation and showing improved crystallization properties. With modern drug-design approaches relying heavily on the elucidation of atomic interactions of potential new drugs with their targets, the need for co-crystal structures with the compounds of interest is high. DXS itself is a promising drug target, as it catalyzes the first reaction in the 2-C-methyl-D-erythritol 4-phosphate (MEP)-pathway for the biosynthesis of the universal precursors of terpenes, which are essential secondary metabolites.