期刊
ANNUAL REVIEW OF BIOCHEMISTRY
卷 76, 期 -, 页码 331-349出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev.biochem.76.062205.122741
关键词
combinatorial chemistry; DNA display; DNA-templated synthesis; in vitro evolution; in vitro selection; small molecules
资金
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [DP1OD000429] Funding Source: NIH RePORTER
- NCCDPHP CDC HHS [1 DP1 0D000429] Funding Source: Medline
In modern academic and industrial laboratories, evolutionary strategies are used routinely to identify biopolymers with novel activities. Large libraries of nucleic acids (similar to 10(15)) or peptides and proteins (similar to 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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