Biomedical Engineering Reference
In-Depth Information
O
N
HN
O
R
3
N
Pilot library of 65
DNA-templated
macrocyclic fumaramides
3'
O
O
R
2
N
H
R
1
O
H
O
Selection for
carbonic anhydrase affinity
O
O
HN
HN
3'
Positive control macrocycle
(1 out of 65 members)
O
HN
O
N
N
H
O
O
O
O
OH
S
NH
2
Nla
III
cleavage
site
NH
4
N
O
Ph
O
sublibraries of DNA-encoded compounds are hybridized, thus generating a large
library in which the pharmacophores are brought together. The resulting library
is then screened for affinity to the target protein, and the high-affinity binders
obtained after washing and removal of unbound molecules are PCR amplified and
decoded on oligonucleotide microarrays. The resulting binding pairs are eventually
linked to a suitable scaffold to yield drug-like molecules. Interestingly, the so-
called ESAC libraries allow identifying high-affinity binders to several proteins of
interest [51-57].
The results discussed in this section have stimulated research efforts to
develop improved or new synthetic and decoding methods related to DNA-encoded
chemical
libraries necessary for
the rapid identification of
lead protein
binders [51,58].
16.4. DNA-BASED ASYMMETRIC CATALYSIS
DNA is one of the most ubiquitous and elegant examples of chirality in Nature. The
induction of chiral effects, such as induced circular dichroism in achiral molecules
interacting with it, is a proof that DNA chirality might be used for other purposes than
DNA replication and RNA transcription [59,60]. Nonetheless, only a few research
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