Approaches to Searching for Hits

At least in academia, HTS capacity is generally limited. In many instances, VS is the only available approach to search for new active compounds. Furthermore, in cases where assays are difficult, time consuming, and/or expensive and hence not straightforward to format for HTS, VS presents a fast and comparably cheap alternative. It is evident that HTS as an individual discipline has not solved the bottlenecks of drug discovery, despite massive investments. Many HTS campaigns are plagued with false-positives and hit sets that are often difficult to deconvolute. There are a number of examples where VS has identified first-in-class active compounds including cases... 

The unpredictability of what components will constitute a successful sensing layer underlines the power of utilizing a 2D combinatorial parallel approach to the discovery of successful sensing systems in aqueous media. The library response toward metal cations can be used to search for either a unique response (individual hit ) or a whole fingerprint of responses. Here, the fingerprint is the collection of the individual responses of each sensing layer to one cation. Rapid inspection of the library fingerprint (Fig. 4.11) provides a unique response for each cation. 

Since Pasteur separated crystalline sodium ammonium tartrate manually in 1848, many researchers have worked on the subject of enantiomeric separation. In 1939 Henderson and Rule fully separated derivatives of camphor by column chromatography using lactose as a stationary phase material [1]. Gil-Av et al. [2] were able to separate amino acid derivatives on a polysiloxane-based stationary phase by gas chromatography (GC) in 1966. Since then many approaches for a successful distinction between enantiomers have been developed for capillary GC and liquid chromatography [3]. It is still a current topic for researchers searching for chiral separation with SciFinder [4] results in 812 hits and searching for chiral recognition leads to 285 hits for the year 2003 only. 

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