Biomedical Engineering Reference
In-Depth Information
11
DNA-ENCODED CHEMICAL
LIBRARIES
LUCA MANNOCCI
11.1
INTRODUCTION
11.1.1 Drug Discovery Today: A Formidable Challenge
The isolation of bioactive molecules is a formidable task in chemistry, biology, and
pharmaceutical sciences. With the advent of the new millennium, sequencing of the
human genome, as well as developments in proteomic research [1,2] and transcrip-
tomic analysis [3,4], have massively aided our understanding of living systems and the
discovery of a multitude of new biological targets associated with human diseases [5].
Biomedical scientists are rapidly gathering increased knowledge of the mechanisms
of diseases; nonetheless, more and more often the elucidation of protein biological
functions requires the availability of highly specific small organic ligands (chemi-
cal genetic approach) [6]. Therefore, the identification of agents capable of specific
binding to validate target proteins remains a major challenge for both academic and
industrial laboratories.
Moreover, with an aging population, biopharmaceutical research is constantly fac-
ing a briskly increasing demand for more and better drugs. Until now, only 10% of the
totally known disease-associated genes have been used in drug discovery campaigns
[7]. Following the quote by Nobel prize-winning J.W. Black, “the most fruitful basis
for the discovery of a new drug is to start with an old drug” [8,9], major pharmaceu-
tical industries appear to spend over U.S.$50 billion per year on R&D to pursue only
a limited number of drug targets. Indeed, omitting biosimilars, salt forms, imaging
agents, and vitamins and other supplements, merely 6% of the over 20,000 drug
 
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