Small‐Molecule Diversification from Iterated Branching Reaction Pathways Enabled by DNA‐Templated Synthesis

Calderone, Christopher T.; Liu, David R.

doi:10.1002/anie.200502899

Cited by 23 publications

(11 citation statements)

References 29 publications

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“…DNA-templated synthesis is emerging as a valuable tool in the implementation of branching pathways. 32 By using a DNA-tagged substrate, a reaction sequence mediated by (DNA-tagged) reactants may be encoded. Remarkably, it is possible for a number of different reaction sequences to be undertaken in the same reaction vessel.…”

Section: Strategies For Diversity-oriented Synthesismentioning

confidence: 99%

Natural products as an inspiration in the diversity-oriented synthesis of bioactive compound libraries

et al. 2008

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Section: Strategies For Diversity-oriented Synthesismentioning

confidence: 99%

Natural products as an inspiration in the diversity-oriented synthesis of bioactive compound libraries

et al. 2008

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“…Multistep synthesis utilizing a variety of linkers and several reaction types has been demonstrated. The synthetic products include tripeptides, branched thioethers (56), a cyclic N-acyloxazolidine (Figure 7a) (52), and a number of products derived from branching reaction pathways (57). The overall yields for these multistep syntheses have fallen between 1% and 10%.…”

Section: Dna-templated Synthesismentioning

confidence: 99%

Chemical Evolution as a Tool for Molecular Discovery

Wrenn

Harbury

2007

Annu. Rev. Biochem.

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In modern academic and industrial laboratories, evolutionary strategies are used routinely to identify biopolymers with novel activities. Large libraries of nucleic acids (approximately 10(15)) or peptides and proteins (approximately 10(13)) can be subjected to multiple rounds of selective pressure, amplification, and diversification, yielding individual sequences with desirable properties. Although the evolutionary approach is a powerful search tool, the chemical nature of biopolymers is not suited for all purposes. Application of evolutionary strategies to libraries of arbitrary chemical composition would overcome this problem, and radically change traditional small-molecule discovery. The chemical make-up of in vitro evolution libraries has necessarily been limited, because library synthesis relies on enzymes. A great deal of current research focuses on expanding the chemical repertoire of in vitro evolution by (a) broadening enzyme substrate specificities to include unnatural building blocks, or (b) developing methods to translate DNA sequences into multistep organic syntheses. We discuss the strengths and weaknesses of the approaches, review the successes, and consider the future of chemical evolution as a tool.

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“…We initiated our study with an N-acylthiazolidine synthesis, which can be assembled with an aldehyde, an aminothiol, and a carboxylic acid. 29,31 We first prepared reagent DNAs (RD1, 41-nt; RD2, 26-nt; RD3, 47-nt; Fig. 2a and Fig.…”

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confidence: 99%