Nucleoside Sensing 英文参考文献.docVIP

Sensors 2006, 6, 860-873 sensors ISSN 1424-8220 ? 2006 by MDPI /sensors Full Research Paper Nucleoside Sensing Michael Fokkens 1, Frank-Gerrit Kl?rner 2,*, Thomas Schrader 1,* 1 Marburg University, Department of Chemistry, Hans-Meerwein-Strasse, 35032 Marburg, Germany. E-mail: schradet@staff.uni-marburg.de 2 Duisburg-Essen University, Institute of Organic Chemistry, Universit?tsstr. 5, 45117 Essen, Germany. E-mail: frank.kl?rner@uni-essen.de * Authors to whom correspondence should be addressed. Received: 5 April 2006 / Accepted: 7 June 2006 / Published: 24 August 2006 Abstract: A rigid molecular clip comprising bisphosphonate binding sites and aromatic sidewalls forming an electron-rich cavity is able to distinguish between nucleosides and nucleotides in aqueous solution. Neutral nucleosides as well as antibiotics derived thereof are drawn into the unpolar interior of the cleft and lead to substantial upfield-shifts in the 1H NMR spectrum. Nucleoside drugs can therefore be detected with high selectivity in the presence of their phosphorylated pendants or nucleic acids. Keywords: Nucleoside, Nucleotide, Molecular Clip, π-Stacking, NMR Sensing. 1. Introduction Nucleoside drugs are of paramount importance in aids or cancer therapy due to their antiviral or antitumor activity. Since it is virtually impossible for highly polar phosphorylated species to pass cell membranes, the respective drugs are administrered as neutral nucleosides, and subsequently activated by intracellular conversion into the 5-triphosphates. A much more elegant approach is the design of Trojan horses, which are masked nucleotides, i. e., neutral lipophilic prodrugs with decreased polarity [1]. However, even for the nucleosides, it is difficult to pass the blood brain barrier [2], so that carrier molecules are needed which may act as potent transporters. The programmed switch between a neutral and a phosphorylated state poses the challeng