Biomedical Engineering Reference
In-Depth Information
(a) Coupling
NH
2
NH
2
NHFmoc
n
NH
2
NH
2
NH
2
POOL
3
5
′
′
5
′
O
(b) Fmoc deprotection
(c) HPLC
NH
3
′
COOH
3
′
5
′
n
n
(ii) 2° reaction
(vi)
COOH
Encoding
SPLIT
m
m
COOH
POOL
(v)
n x m member
DNA-encoded chemical library
FIGURE 11.7
Schematic representation of the split-pool-split approach pioneered by Philochem for the construction of single-pharmacophore
DNA-encoded chemical libraries based on two sets of building blocks. The strategies feature (i) conjugation of the first set of chemical compounds
(e.g.,
n
Fmoc amino acids) to distinct amino-modified oligonucleotides, followed by Fmoc removal and HPLC purification; (ii) pooling of the reactions
and splitting into
m
separate reaction vessels, corresponding to the reactions for the insertion of the second building block; (iii) chemical incorporation
of the second building block; (iv) encoding of the second building block (e.g., by hybridization of partially complementary oligonucleotides, followed
by Klenow fragment-mediated DNA polymerization); (v) pooling of the encoded reactions to yield a DNA-encoded chemical library containing
n
×
m
molecules. (From [54]: copyright
C
2008 National Academy of Sciences, U.S.A.) (
See insert for color representation of the figure.
)
