Multiple cleavable linkers

Lebl [121,130-134] and Baldwin [126,127] first reported an efficient strategy, in which the advantages of performing assays in solution and structural determination of resin-bound compounds are combined. This method is based on multiple cleavable linkers which can release aliquots of the resin-bound compound, rather than cleaving all the compound bound to one resin bead at once. 

Figure 1.11. Screening scheme of combinatorial libraries by the use of multiple cleavable linkers Two-stage screening and then identification of the biologically active compound.

Structurally complex molecules are prepared by multistep reactions. The Q architecture and distance-independent reactions have enabled a single DNA template to direct multiple reactions at different regions. However, after eaeh reaction, strategies need to be developed to remove the reagent DNA strand and to purify the template-linked product from unreacted template in preparation for the next step. A variety of cleavable linker strategies and solid-phase-based affinity purification have been developed to address these two key aspects of multistep DNA-template synthesis. 

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