PMID: 9427663Mar 7, 1998Paper

Small molecule-dependent genetic selection in stochastic nanodroplets as a means of detecting protein-ligand interactions on a large scale

Chemistry & Biology
A BorchardtS L Schreiber

Abstract

Understanding the cellular role of a protein often requires a means of altering its function, most commonly by mutating the gene encoding the protein. Alternatively, protein function can be altered directly using a small molecule that binds to the protein, but no general method exists for the systematic discovery of small molecule ligands. Split-pool synthesis provides a means of synthesizing vast numbers of small molecules. Synthetic chemists will soon be able to synthesize natural product-like substances by this method, so compatible screening methods that detect the activity of minute quantities of molecules among many inactive ones will be in demand. We describe two advances towards achieving the above goals. First, a technique is described that uses a simple spray gun to create 5000-8000 droplets randomly, each having a volume of 50-200 nanoliters. The individual 'nanodroplets' contain a controlled number of cells and many also contain individual synthesis beads. As small molecules can be photochemically released from the beads in a time-dependent manner, the concentration of ligands that the cells are exposed to can be controlled. The spatial segregation of nanodroplets prevents the mixing of compounds from other beads so...Continue Reading

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Citations

Aug 26, 1999·Trends in Biotechnology·M Vidal, H Endoh
Sep 30, 1998·Current Opinion in Biotechnology·L M Kauvar, H O Villar
Oct 24, 1998·Bioorganic & Medicinal Chemistry·S L Schreiber
Oct 18, 2000·Journal of Pharmacological and Toxicological Methods·C K JayawickremeJ Shaffer
Mar 24, 2000·Drug Discovery Today·G R LenzS Jindal
Sep 13, 2003·Current Opinion in Chemical Biology·Julia Khandurina, András Guttman
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Dec 15, 2010·Journal of the American Chemical Society·Nobuhiro UmedaTakanari Inoue
Mar 20, 2001·Nature Reviews. Genetics·B R Stockwell
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·D C ChanP S Kim
Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·K M SakamotoR J Deshaies
Jan 28, 2016·Analytical Chemistry·Alexander K PriceBrian M Paegel
Jul 5, 2005·Expert Opinion on Investigational Drugs·M Navre
Aug 22, 2001·Chemistry & Biology·C P ScottS J Benkovic
Jul 8, 1998·Chemistry & Biology·C Denison, T Kodadek
Jun 9, 2016·ACS Chemical Biology·Dries J H De ClercqSerge Van Calenbergh
Feb 16, 2017·ACS Combinatorial Science·Andrew B MacConnellBrian M Paegel
Jun 12, 2018·Chemical Communications : Chem Comm·Vitaly V KomnatnyyKatrine Qvortrup
Mar 18, 2010·Chemical Communications : Chem Comm·Grégory UpertHelma Wennemers
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Mar 20, 2009·Journal of Inorganic Biochemistry·Khairul I AnsariSubhrangsu S Mandal
Nov 23, 2021·ACS Chemical Biology·Wesley G CochraneBrian M Paegel

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