A nanolithographic approach based on hierarchical peptide self-assembly is presented. An aromatic peptide of N-(t-Boc)-terminated triphenylalanine is designed from a structural motif for the beta-amyloid associated with Alzheimer's disease. This peptide adopts a turnlike conformation with three phenyl rings oriented outward, which mediate intermolecular pi-pi stacking interactions and eventually facilitate highly crystalline bionanosphere assembly with both thermal and chemical stability. The self-assembled bionanospheres spontaneously pack into a hexagonal monolayer at the evaporating solvent edge, constituting evaporation-induced hierarchical self-assembly. Metal nanoparticle arrays or embossed Si nanoposts could be successfully created from the hexagonal bionanosphere array masks in conjunction with a conventional metal-evaporation or etching process. Our approach represents a bionanofabrication concept that biomolecular self-assembly is hierarchically directed to establish a straightforward nanolithography compatible with conventional device-fabrication processes.

Chiral beta-substituted gamma-butyrolactones are known to be important intermediates for many biologically active compounds such as gamma-aminobutyric acid (GABA) derivatives and lignans. We have developed a general, convenient, and scalable synthetic method for enantiomerically pure beta-substituted gamma-butyrolactones, with either configuration, via nucleophilic cyclopropane ring opening of (1S,5R)- or (1R,5S)-bicyclic lactone followed by decarbethoxylation. The utility of our method was demonstrated by streamlined synthesis of pregabalin ((S)-3-isobutyl-gamma-aminobutyric acid), an anticonvulsant drug for the treatment of peripheral neuropathic pain.

No abstract

ABSTRACT:We identified a novel class of aryl-substituted triazine compounds as potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) during a high-throughput screening campaign that evaluated more than 200000 compounds for antihuman immunodeficiency virus (HIV) activity using a cell-based full replication assay. Herein, we disclose the optimization of the antiviral activity in a cell-based assay system leading to the discovery of compound 27, which possessed excellent potency against wild-type HIV-1 (EC 50 = 0.2 nM) as well as viruses bearing Y181C and K103N resistance mutations in the reverse transcriptase gene. The X-ray crystal structure of compound 27 complexed with wild-type reverse transcriptase confirmed the mode of action of this novel class of NNRTIs. Introduction of a chloro functional group in the pyrazole moiety dramatically improved hERG and CYP inhibition profiles, yielding highly promising leads for further development.