Figure 5.

Schematic representation of encoding strategies for DNA-templated synthesis of chemical libraries. (a) An oligonucleotide template (here depicted for the construction of a molecule based on two building blocks) is annealed with a chemically modified oligonucleotide, which transfers a chemical moiety to the nascent molecule. At the end of the coupling step, the cleavable connection between the building block B and the corresponding oligonucleotide (depicted with a dotted line). (b) In a modified procedure, a general template (containing poly-I stretches for annealing with various coding segments) is sequentially hybridized with oligonucleotide derivatives, which transfer building blocks onto a nascent molecule. (c) In YoctoReactor™ technology, hairpin structures (containing a coding sequence and a building block, are used to mediate successive cycles of DNA ligation and of chemical reactions. Cleavable linkers are indicated with a dotted line. (d) In DNA routing strategies, long oligonucleotides (containing multiple coding sequences) are sequentially hybridized to columns carrying complementary oligonucleotides. Individual column hybridization steps dictate which chemical reaction (i.e., which building block addition) is performed on a given nascent molecule.