Encoding methods

A wide variety of encoding methods have been developed to record the history of a bead used in the Furka mix and split technique. This section outlines some of these methods. 

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This structure encoding method has been applied both for the classification of a data set comprising 31 corticosteroids, for which affinity data were available in the literature, binding to the corticosteroid-binding globulin (CBG) receptor, and for the simulation of infrared spectra [28, 29). 

An entirely different type of transport is formed by thermal convection and conduction. Flow induced by thermal convection can be examined by the phaseencoding techniques described above [8, 44, 45] or by time-of-flight methods [28, 45]. The latter provide less quantitative but more illustrative representations of thermal convection rolls. The origin of any heat transport, namely temperature gradients and spatial temperature distributions, can also be mapped with the aid of NMR techniques. Of course, there is no direct encoding method such as those for flow parameters. However, there are a number of other parameters, for example, relaxation times, which strongly depend on the temperature so that these parameters can be calibrated correspondingly. Examples are described in Refs. [8, 46, 47], for instance. 

The short signal lifetimes of these nuclei (bulk T2 around a hundred ps and T) around a few ms) [14] require the use of pure phase encode methods. The low concentration of these nuclei coupled with the low absolute sensitivity requires a measurement technique that is rapid enough to permit numerous signal averages. 

A W. Czamik, Encoding Methods for Combinatorial Chemistry , Cun. Opin. Chem Biol 1997, X 60-66. 

The phase-encoding methods are considered to be the most robust and quantitative but, as demonstrated below, TOF and rapid image acquisition can be particularly useful in specific applications. 

To test whether a polypeptide or other compound carried on a given bead has a derived biological activity, such as the ability to inhibit a certain enzyme, various assays that require only one bead can be devised. However, if a particular bead carries a compound of interest, how can it be identified The bead carries only a small amount of compound but it may be possible using microsequencing procedures to identify it. An alternative procedure is to use an encoding method to identify the beads. 

Very recently, we reported on a novel chemical encoding method that uses separate coding tags with a cleavable linker in the bead interior. These coding tags can be released for decoding with mass spectrometry.16... 

Outline the range of encoding methods used to deduce the structures of compounds produced in a Furka mix and split combinatorial synthesis. 

The encoding constructs used require many additional molecules, such as glycine alanine, lysine and so on, which may prove sensitive to some reaction conditions for library synthesis. The physical bulk of the encoding moieties may also hinder the reactivity of some library intermediates, or produce side reactions which decrease the library quality and cannot be detected by the encoding method, or disturb on-bead screening, preventing or hindering... 

Another group of researchers recently reported the validation of a similar 19F NMR-based encoding method [60]. 

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