Systems-Based Design of Bi-Ligand Inhibitors of Oxidoreductases: Filling the Chemical Proteomic Toolbox

Genomics-driven growth in the number of enzymes of unknown function has created a need for better strategies to characterize them. Since enzyme inhibitors have traditionally served this purpose, we present here an efficient systems-based inhibitor design strategy, enabled by bioinformatic and NMR structural developments. First, we parse the oxidoreductase gene family into structural subfamilies termed pharmacofamilies, which share pharmacophore features in their cofactor binding sites. Then we identify a ligand for this site and use NMR-based binding site mapping (NMR SOLVE) to determine where to extend a combinatorial library, such that diversity elements are directed into the adjacent substrate site. The cofactor mimic is reused in the library in a manner that parallels the reuse of cofactor domains in the oxidoreductase gene family. A library designed in this manner yielded specific inhibitors for multiple oxidoreductases

Fabrication, structure and properties of epoxy/metal nanocomposites

Gd2O3 nanoparticles surface-modified with IPDI were compounded with epoxy. IPDI provided an anchor into the porous Gd2O3 surface and a bridge into the matrix, thus creating strong bonds between matrix and Gd2O3. 1.7 vol.-% Gd2O3 increased the Young’s modulus of epoxy by 16–19%; the surface-modified Gd2O3 nanoparticles improved the critical strain energy release rate by 64.3% as compared to 26.4% produced by the unmodified nanoparticles. The X-ray shielding efficiency of neat epoxy was enhanced by 300–360%, independent of the interface modification. Interface debonding consumes energy and leads to crack pinning and matrix shear banding; most fracture energy is consumed by matrix shear banding as shown by the large number of ridges on the fracture surface

Spin Caloritronics

This is a brief overview of the state of the art of spin caloritronics, the science and technology of controlling heat currents by the electron spin degree of freedom (and vice versa).Comment: To be published in "Spin Current", edited by S. Maekawa, E. Saitoh, S. Valenzuela and Y. Kimura, Oxford University Pres