Biomedical Engineering Reference
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FIGURE 11.14 General scheme for DNA-templated synthesis of DNA-encoded macrocyclic libraries. A discrete number of DNA-linked scaffolds
simultaneously undergo three DNA-programmed reaction steps (two acylations sNHS/EDC mediated and one Wittig macrocyclization) with different
DNA-templated reagents, yielding the final single-stranded DNA-encoded macrocyclic library. Conjugate intermediates are purified by affinity capture
on avidin (or streptavidin) resins and elution in denaturing conditions. Scarless linkers (i.e., base labile sulfone linkers) allow the introduction of
suitable functional groups for the next reaction step, while autocleaving linkers are used to trigger macrocyclic ring-closure reaction at the end of
library assembly.
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