6-Pyrazolylpurine and its deaza derivatives as nucleobases for silver(I)-mediated base pairing with pyrimidines.

The artificial nucleobase 6-pyrazolylpurine (6PP) and its deaza derivatives 1-deaza-6-pyrazolylpurine (6PP), 7-deaza-6-pyrazolylpurine (6PP), and 1,7-dideaza-6-pyrazolylpurine (6PP) were investigated with respect to their ability to differentiate between the canonical nucleobases cytosine and thymine by means of silver(I)-mediated base pairing. As shown by temperature-dependent UV spectroscopy and by circular dichroism spectroscopy, 6PP and (to a lesser extent) 6PP form stable silver(I)-mediated base pairs with cytosine, but not with thymine. 6PP and 6PP do not engage in the formation of stabilizing silver(I)-mediated base pairs with cytosine or thymine.

Metal-dependent electrochemical discrimination of DNA quadruplex sequences.

Films of four different DNA quadruplex-forming (G4) sequences (c-KIT, c-MYC, HTelo, and BCL2) on gold surfaces were investigated by electrochemical impedance spectroscopy (EIS) to evaluate whether they evoke unique electrochemical responses that can be used for their identification. This could render EIS an alternative means for the determination of G4 sequences of unknown structure. Towards, this end, cation-dependent topology changes in the presence of either K, K in combination with Li, or Pb in the presence of Li were first evaluated by circular dichroism (CD) spectroscopy, and electrochemical studies were performed subsequently.

Silver(I) Coordination in Silver(I)-Mediated Homo Base Pairs of 6-Pyrazolylpurine in DNA Duplexes Involves the Watson-Crick Edge.

DNA duplexes comprising 6-(1H-pyrazol-1-yl)-9H-purine (6PP), 1-deaza-6PP ( 6PP), 7-deaza-6PP ( 6PP) and 1,7-dideaza-6PP ( 6PP) 2'-deoxyribonucleosides, respectively, were investigated towards their ability to form metal-mediated base pairs in the presence of Ag . In 6PP and 6PP, the Ag ion can coordinate to the nucleobase via the endocyclic N1 nitrogen atom, that is, via the Watson-Crick edge. In contrast, this nitrogen atom is not available in 6PP and 6PP, so that in 6PP an Ag coordination is only possible via the Hoogsteen edge (N7).

Dedicated, Persistent, Knowledgeable, Visionary and Smart: Dr. Oreste Ghisalba Helped Leverage the Great Potential of Biotechnology to the Benefit of Switzerland.

Oreste Ghislaba's powerful vision and actions to make Switzerland a world-leading hub in biotechnology are described. He recognised the great potential for innovation in biotechnology and was able to communicate this to stakeholders in academia, industry and politics. He was instrumental in the creation of organisations such as Swiss Biotech Association, the CTI, the SATW, TA-Swiss, and the Swiss Industrial Biocatalysis Consortium that helped to create the Swiss biotech hub.

Single-Chain Antibody Fragment VEGF Inhibitor RTH258 for Neovascular Age-Related Macular Degeneration: A Randomized Controlled Study.

Purpose: To assess the safety and efficacy of different doses of RTH258 applied as single intravitreal administration compared with ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (AMD).

Design: Six-month, phase 1/2, prospective, multicenter, double-masked, randomized, ascending single-dose, active-controlled, parallel-group study.