DNA-templated library

In this chapter, we will first discuss the basic principles of DNA-templated organic synthesis, as it is the mechanistic foundations for DNA-encoded libraries then we will discuss the progressive development of DNA-templated libraries and the evolution into a novel drug discovery tool. We will also discuss the DNA-recorded library, which also encodes library molecules with DNA but is conceptually different. These discussions will naturally involve specific drug discovery programs in which these libraries were applied and finally, we will discuss the outlook of DNA-eneoded libraries in the future of drug discovery. 

In a DNA-templated library, the DNA template serves two purposes. First, it is a nano-reactor virtually separated from each other spatially so that parallel reactions can proceed simultaneously. Second, it encodes the information of the specific chemical structure to be synthesized on the template in form of DNA sequences. In other words, the sequence of each template pre-determines the specific structures to be synthesized on it. This is analogous to the genetic information translation from mRNA to proteins the sequence of a particular mRNA determines the specific protein synthesized on it. This feature differentiates a DNA-templated library from other types of DNA-encoded libraries, which will be discussed in later sections. 

Figure 8,8 Scheme for the construction of DNA-templated libraries and identification of active molecules after selection. Reprinte permission from Ensemble Discovery. 

The ultimate goal of creating a DNA-templated library is to interrogate protein targets. Due to the poor cell permeability of DNA-conjugated molecules, a DNA-templated library is mostly suitable for in vitro selection of purified proteins based on alfinity. 

Figure 8.15 Three-dimensional plot of DNA-templated library before and after selection. Each ball represents a unique compound structure in the library. After selection, hits are identified and the enrichment fold is represented by different colors. Reprinted with permission from Ensemble Discovery.

Harbury s DNA routing method in synthesizing DNA-template libraries.Reprinted, with permission, from Wrenn et al. 2007 American Chemical Society. 

Nuevolution is a company located in Denmark and has been developing DNA-templated libraries since 2001. Nuevolution holds a number of patents and patent applications on their technology named Chemetics . Throughout Nuevolution s patent filings, there are many different presentations on how... 

DNA-templated Library by DNA Junction Formation Vipergen and YoctoReactor ... 

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