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Highly parallel translation of DNA sequences into small molecules

Weisinger, Rebecca M ; Wrenn, S Jarrett ; Harbury, Pehr B Romesberg, Floyd

PloS one, 2012-03, Vol.7 (3), p.e28056-e28056 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Highly parallel translation of DNA sequences into small molecules
Autor: Weisinger, Rebecca M ; Wrenn, S Jarrett ; Harbury, Pehr B
Romesberg, Floyd
Assuntos: Affinity ; Biochemistry ; Biological evolution ; Biology ; Biopolymers ; Cell permeability ; Chemistry ; Combinatorial analysis ; Combinatorial chemistry ; Combinatorial Chemistry Techniques - instrumentation ; Combinatorial Chemistry Techniques - methods ; Deoxyribonucleic acid ; Devices ; DNA ; DNA - genetics ; DNA polymerase ; DNA sequencing ; Engineering ; Evolution ; Evolution (Biology) ; Experiments ; Gene Library ; Gene sequencing ; Genes ; Genetic research ; Hydrogen ; Hydrogen bonds ; Hydrophobicity ; Immunogenicity ; Library collections ; Ligands ; Mass production ; Medical research ; Medical screening ; Microfluidic Analytical Techniques - instrumentation ; Microfluidic Analytical Techniques - methods ; Nucleotide sequence ; Nucleotide sequencing ; Permeability ; Physical properties ; Protein Biosynthesis - genetics ; Proteins ; Reproducibility of Results ; Small Molecule Libraries
É parte de: PloS one, 2012-03, Vol.7 (3), p.e28056-e28056
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Current address: Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, USA
Conceived and designed the experiments: RMW SJW PBH. Performed the experiments: RMW PBH. Analyzed the data: RMW PBH. Wrote the paper: RMW PBH.
Descrição: A large body of in vitro evolution work establishes the utility of biopolymer libraries comprising 10(10) to 10(15) distinct molecules for the discovery of nanomolar-affinity ligands to proteins. Small-molecule libraries of comparable complexity will likely provide nanomolar-affinity small-molecule ligands. Unlike biopolymers, small molecules can offer the advantages of cell permeability, low immunogenicity, metabolic stability, rapid diffusion and inexpensive mass production. It is thought that such desirable in vivo behavior is correlated with the physical properties of small molecules, specifically a limited number of hydrogen bond donors and acceptors, a defined range of hydrophobicity, and most importantly, molecular weights less than 500 Daltons. Creating a collection of 10(10) to 10(15) small molecules that meet these criteria requires the use of hundreds to thousands of diversity elements per step in a combinatorial synthesis of three to five steps. With this goal in mind, we have reported a set of mesofluidic devices that enable DNA-programmed combinatorial chemistry in a highly parallel 384-well plate format. Here, we demonstrate that these devices can translate DNA genes encoding 384 diversity elements per coding position into corresponding small-molecule gene products. This robust and efficient procedure yields small molecule-DNA conjugates suitable for in vitro evolution experiments.
Editor: United States: Public Library of Science
Idioma: Inglês

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Highly parallel translation of DNA sequences into small molecules

Weisinger, Rebecca M ; Wrenn, S Jarrett ; Harbury, Pehr B Romesberg, Floyd

United States: Public Library of Science

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