Optimized Inhibitors of MDM2 via an Attempted Protein-Templated Reductive Amination

Innovative and efficient hit-identification techniques are required to accelerate drug discovery. Protein-templated fragment ligations represent a promising strategy in early drug discovery, enabling the target to assemble and select its binders from a pool of building blocks. Development of new protein-templated reactions to access a larger structural diversity and expansion of the variety of targets to demonstrate the scope of the technique are of prime interest for medicinal chemists. Herein, we present our attempts to use a protein-templated reductive amination to target protein-protein interactions (PPIs), a challenging class of drug targets. We address a flexible pocket, which is difficult to achieve by structure-based drug design. After careful analysis we did not find one of the possible products in the kinetic target-guided synthesis (KTGS) approach, however subsequent synthesis and biochemical evaluation of each library member demonstrated that all the obtained molecules inhibit MDM2. The most potent library member (Ki=0.095 μm) identified is almost as active as Nutlin-3, a potent inhibitor of the p53-MDM2 PPI

Quantum Characterization of a Werner-like Mixture

We introduce a Werner-like mixture [R. F. Werner, Phys. Rev. A {\bf 40}, 4277 (1989)] by considering two correlated but different degrees of freedom, one with discrete variables and the other with continuous variables. We evaluate the mixedness of this state, and its degree of entanglement establishing its usefulness for quantum information processing like quantum teleportation. Then, we provide its tomographic characterization. Finally, we show how such a mixture can be generated and measured in a trapped system like one electron in a Penning trap.Comment: 8 pages ReVTeX, 8 eps figure

AVALIAÇÃO DA IMUNIZAÇÃO COM CATEPSINA L3 FRENTE À FASCIOLOSE EXPERIMENTAL

Fasciolose acomete principalmente bovinos e ovinos e é responsável por importantes perdas econômicas. Objetivou-se testar em ratos e bovinos a proteção do antígeno recombinante Catepsina L3 frente à infecção experimental por Fasciola hepatica. Os ratos foram divididos nos grupos: 1) imunizados; 2) adjuvante e 3) controle. Os bovinos foram divididos nos grupos: 4) imunizados e 5) adjuvante. Avaliaram-se ovos por grama nas fezes e contagem parasitária nos ratos, ganho de peso diário e contagem parasitária nos bovinos. Observou-se baixo índice de proteção, não alcançando nível suficiente para utilização comercial do antígeno