Chemical encoding strategies rely on the assumption that the chemical analysis of a given member of the library is more difficult than the analysis of a chemical tag. In most cases this assumption is valid and justifies the described technique. Some libraries have been prepared and characterized by individual mass spectroscopic analysis of each member of the library. However, to obtain unambiguous results, the following criteria must be fulfilled:
1. Each member of the library must have a different molecular weight.
2. The compounds must ionize, without destruction into the gas phase.
These requirements seem to be rather limiting, but a synthetic linker to a solid support was recently described which enhances ejection of the product upon laser irradiation in the MALDI instrument . Another approach relies on isotopically different reagents .
Due to the aforementioned limiting factors, spectroscopic encoding is not broadly applicable and is used only rarely for the encoding of libraries.
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