“Scaffold-Hopping” by Topological Pharmacophore Search: A Contribution to Virtual Screening

A chemically advanced template search (CATS) based on topological pharmacophore models has been developed as a technique for virtual screening. This technique has successfully identified novel potent Ca²⁺ antagonists (such as 2 ) that have a similar activity to 1 (a known T-channel blocking agent) in a library of several hundred thousand compounds on the basis of a correlation vector representation.     

Frequency Lock of an Optically Pumped FIR Ring Laser at 803 and 1626 GHz

We report an automatic frequency control (AFC) for an optically pumped far infrared (FIR) ring laser applicable for high resolution THz sideband spectroscopy by mixing a fraction of the laser power and a harmonic of a phase-locked synthesizer on a planar Schottky diode. We achieve a relative frequency accuracy of about 0.5 kHz rms at 803 GHz ( ¹⁵ NH ₃ ) and about 1 kHz rms at 1626.6 GHz (CH ₂ F ₂ ) over hours of lock time. The absolute frequency accuracy is estimated to be about 5 kHz at 1626.6 GHz.     

Molecular Gears: From Solution to Surfaces

This review highlights the major efforts devoted to the development of molecular gears over the past 40 years, from pioneering covalent bis-triptycyl systems undergoing intramolecular correlated rotation in solution, to the most recent examples of gearing systems anchored on a surface, which allow intermolecular transmission of mechanical power. Emphasis is laid on the different strategies devised progressively to control the architectures of molecular bevel and spur gears, as intramolecular systems in solution or intermolecular systems on surfaces, while aiming at increased efficiency, complexity and functionality.     

Discovery of small-molecule interleukin-2 inhibitors from a DNA-encoded chemical library

Libraries of chemical compounds individually coupled to encoding DNA tags (DNA-encoded chemical libraries) hold promise to facilitate exceptionally efficient ligand discovery. We constructed a high-quality DNA-encoded chemical library comprising 30,000 drug-like compounds; this was screened in 170 different affinity capture experiments. High-throughput sequencing allowed the evaluation of 120?million DNA codes for a systematic analysis of selection strategies and statistically robust identification of binding molecules. Selections performed against the tumor-associated antigen carbonic anhydrase?IX (CA?IX) and the pro-inflammatory cytokine interleukin-2 (IL-2) yielded potent inhibitors with exquisite target specificity. The binding mode of the revealed pharmacophore against IL-2 was confirmed by molecular docking. Our findings suggest that DNA-encoded chemical libraries allow the facile identification of drug-like ligands principally to any protein of choice, including molecules capable of disrupting high-affinity protein-protein interactions.