DNA-ENCODED CHEMICAL LIBRARIES - Diversity-Oriented Synthesis - page 382

(a)

3 ′ 5 ′

3 ′ 5 ′

5 ′ 3 ′

5 ′ 3 ′

DNA-directed
reaction

3 ′

5 ′

3 ′

5 ′

5 ′ 3 ′

5 ′

3 ′

Non-cleavable
linker
a

(b)

a x b

1. Annealing
2. DNA-directed
reaction

1. Annealing
2. DNA-directed
reaction

1. Purification
2. Ligation

b

3. Linker cleavage

Cleavable linker

c

1. Purification
2. Ligation

Single round
PCR

3. Linker cleavage

a x b x c DNA-encoded library

(c)

a

b

Library assembling

c

Next round

“rolling translation”

Selection

PCR-amplification

FIGURE 11.18 Vipergen's YoctoReactor technology. (a) A highly stable three-dimensional
DNA complex (DNA junction) confines DNA-conjugate reagents within a volume on the order
of 10 − 24 liter (yoctoliter). By means of the proximity effect, DNA-directed reactions take place
at the center of the molecular reactor, delivering the corresponding building blocks on the initial
reaction site. (b) Synthesis of a three-way DNA-encoded chemical library. Individual building
blocks are linked via cleavable or noncleavable linkers to distinct hairpin-shaped DNA