Biomedical Engineering Reference
In-Depth Information
FIGURE 11.2 Analogy of a display technology (e.g., antibody phage display) and DNA-
encoded chemical libraries. (a) Antibody fragment displayed in scFv format as a fusion protein
to the pIII protein on the tip of the phage particle. The phage particle provides physical linkage
between the protein-binding properties (phenotype) and the genetic information coding for the
antibody (genotype). (b) DNA-encoded chemical libraries as a conceptual translation of the
antibody phage display technology. Small organic molecules are covalently linked to unique
DNA-oligonucleotides. The DNA tag (genotype) serves as an amplifiable identification bar
code for the small organic molecule displayed (phenotype). (From [44], with permission of
The Royal Society of Chemistry.)
as a whole, the achievements, current challenges, and outlooks of DNA-encoded
chemical library technology are discussed.
11.2 DNA-ENCODED CHEMICAL LIBRARIES
11.2.1 DNA Encoding
Following the revolutionary discovery of the DNA structure by Watson and Crick
in 1953 [45,46], scientists have been immediately fascinated by its amenable prop-
erties toward manipulation, hybridization, amplification, and sequencing. To date,
researchers have pioneered the implementation of these principles from nanotechnol-
ogy and material sciences, to chemical biology and drug discovery, far beyond their
natural functions.
In 1992, inspired by the covalent linkage between the DNA genotype and antibody
phenotype of display technologies such as phage display, Brenner and Lerner intro-
duced the concept of associating PCR-amplifiable DNA-base identification tags with
synthetic chemotypes (e.g., small organic molecules) to facilitate the identification
of biologically active compounds after affinity-based selection experiments [47].
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