Structure-Based Design of Non-Natural Amino Acid Inhibitors of Amyloid Fibrillation

Many globular and natively disordered proteins can convert into amyloid fibers. These fibers are associated with numerous pathologies1 as well as with normal cellular functions2,3, and frequently form during protein denaturation4,5. Inhibitors of pathological amyloid fibers could serve as leads for therapeutics, provided the inhibitors were specific enough to avoid interfering with normal processes. Here we show that computer-aided, structure-based design can yield highly specific peptide inhibitors of amyloid formation. Using known atomic structures of segments of amyloid fibers as templates, we have designed and characterized an all D-amino acid inhibitor of fibrillation of the tau protein found in Alzheimer’s disease, and a non-natural L-amino acid inhibitor of an amyloid fiber that enhances sexual transmission of HIV. Our results indicate that peptides from structure-based designs can disrupt the fibrillation of full-length proteins, including those like tau that lack fully ordered native structures.We thank M.I. Ivanova, J. Corn, T. Kortemme, D. Anderson, M.R. Sawaya, M. Phillips, S. Sambashivan, J. Park, M. Landau, Q. Zhang, R. Clubb, F. Guo, T. Yeates, J. Nowick, J. Zheng, and M.J. Thompson for discussions, HHMI, NIH, NSF, the GATES foundation, and the Joint Center for Translational Medicine for support, R. Peterson for help with NMR experiments, E. Mandelkow for providing tau constructs, R. Riek for providing amyloid beta, J. Stroud for amyloid beta preparation. Support for JK was from the Damon Runyon Cancer Research Foundation, for HWC by the Ruth L. Kirschstein National Research Service Award, for JM from the programme for junior-professors by the ministry of science, Baden-Württemberg, and for SAS by a UCLA-IGERT bioinformatics traineeship

Transfusion-transmitted infections

Although the risk of transfusion-transmitted infections today is lower than ever, the supply of safe blood products remains subject to contamination with known and yet to be identified human pathogens. Only continuous improvement and implementation of donor selection, sensitive screening tests and effective inactivation procedures can ensure the elimination, or at least reduction, of the risk of acquiring transfusion transmitted infections. In addition, ongoing education and up-to-date information regarding infectious agents that are potentially transmitted via blood components is necessary to promote the reporting of adverse events, an important component of transfusion transmitted disease surveillance. Thus, the collaboration of all parties involved in transfusion medicine, including national haemovigilance systems, is crucial for protecting a secure blood product supply from known and emerging blood-borne pathogens

Single‐step spray printing of symmetric all‐organic solid‐state batteries based on porous textile dye electrodes

A symmetric solid-state battery based on organic porous electrodes is fabricated using scalable spray-printing. The active electrode material is based on a textile dye (disperse blue 134 anthraquinone) and is capable of forming divalent cations and anions in oxidation and reduction processes. The resulting molecule can be used in both negative and positive electrode reactions. After spray printing an inter-connected pore honeycomb electrode, a solid-state electrolyte (σLi: × 10−4 S cm−1) based on a polymeric ionic liquid is spray-printed as a second layer and infiltrated through the porous electrodes. A symmetric all-organic battery is then formed with the addition of another identical set of electrode and electrolyte layers. Both density functional theory calculations and charge-discharge profiles show that the potentials for the negative and positive electrode reactions are amongst the lowest (≈2.0 V vs Li) and the highest (≈3.5 V vs Li), respectively, for quinone-type molecules. Over the C-rate range 0.2 to 5 C, the battery has a discharge cell voltage of more than 1 V even up to 250 charge-discharge cycles and capacities are in the range 50–80 mA h g−1 at 0.5 C