Biomedical Engineering Reference
In-Depth Information
sampling problems associated with high-throughput-sequencing decoding (e.g., the
library results being much larger than the number of DNA sequences that can be
efficaciously sequenced) and the drug-likeness of the final molecular candidates (see
also Section 11.5).
It is worth noting that library size and chemical diversity of the compounds
displayed depend exclusively on the number of split-pool cycles and building blocks
introduced during library assembly. Therefore, size and diversity are typically gained
at the expense of a growing molecular weight and decreasing library quality, due
to incomplete reactions (Figure 11.11). Eventually, smaller libraries, comprising up
to a few millions of compounds, are intrinsically of superior quality and typically
contain compounds that may better fulfill drug-like criteria such as Lipinski's rule
FIGURE 11.11
Molecular weight and log
P
distribution of two different single-
pharmacophore DNA-encoded chemical libraries. (a) Two building blocks single-pharma-
cophore DNA-encoded library containing 30.000 compounds; (b) single-pharmacophore DNA-
encoded library based on three building blocks comprising 1.7 million compounds. Small
libraries are intrinsically of superior quality and contain compounds that may better fulfill
drug-like criteria. (From [44], with permission of The Royal Society of Chemistry.)
