Erratum: Design, synthesis and selection of DNA-encoded small-molecule libraries

Acharya, Raksha A; Belyanskaya, Svetlana; Benjamin, Dennis R.; Carlson, Neil R; Centrella, Paolo A.; Chiu, Cynthia H.; Creaser, Steffen P.; Cuozzo, John W.; Davie, Christopher P.; Ding, Yun; Franklin, G Joseph; Franzen, Kurt D; Gefter, Malcolm L.; Hale, Steven P; Hansen, Nils Jakob Vest; Israel, David I.; Jiang, Jinwei; Kavarana, Malcolm J.; Kelley, Michael S. P.; Kollmann, Christopher; Li, Fan; Lind, Kenneth; Mataruse, Sibongile; Medeiros, Patricia F; Messer, Jeffrey A.; Myers, Paul; O’Keefe, Heather; Oliff, Matthew C; Rise, Cecil; Satz, Alexander L.; Skinner, Steven R.; Svendsen, Jennifer L; Tang, Lujia; Vloten, Kurt van; Wagner, Richard W.; Yao, Gang; Zhao, Baoguang; Morgan, Barry A.

doi:10.1038/nchembio1009-772

Cited by 9 publications

(10 citation statements)

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“…The vast majority of chemicals are fine chemicals produced at small or very small scale, with an emphasis on quality and purity. An ultimate example is the synthesis of highly-diverse combinatorial libraries containing billions of different structures with as few as 1000 copies of every structure [4]. Until recently, batch production of fine chemicals was the only available option.…”

Section: Small-scale Continuous-flow Synthesismentioning

confidence: 99%

Advances in steady-state continuous-flow purification by small-scale free-flow electrophoresis

Agostino

Krylov

2015

TrAC Trends in Analytical Chemistry

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Section: Small-scale Continuous-flow Synthesismentioning

confidence: 99%

Advances in steady-state continuous-flow purification by small-scale free-flow electrophoresis

Agostino

Krylov

2015

TrAC Trends in Analytical Chemistry

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“…DNA-Encoded Library (DEL) technology is based on the concept from Brenner and Lerner ( Brenner and Lerner 1992 ) and it is commonly used in the pharmaceutical industry to identify novel chemical matter that binds and modulates specific protein targets ( Melkko et al, 2004 ; Melkko et al, 2007 ; Clark et al, 2009 ; Kleiner et al, 2011 ; Franzini et al, 2014 ; Salamon et al, 2016 ; Goodnow et al, 2017 ; Favalli et al, 2018 ; Neri and Lerner 2018 ; Ottl et al, 2019 ; Yuen et al, 2019 ; Zhao et al, 2019 ; Kunig et al, 2021 ; Shi et al, 2021 ). During the past decade, the use of DEL technology provided a great opportunity to identify drug-like compounds that can bind selectively to a variety of target proteins ( Deng et al, 2012 ; Gentile et al, 2012 ; Disch et al, 2013 ; Samain et al, 2015 ; Seigal et al, 2015 ; Harris et al, 2016 ; Belyanskaya et al, 2017 ; Dawadi et al, 2020 ; Chamakuri et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

DNA-Compatible Suzuki-Miyaura Cross-Coupling Reaction of Aryl Iodides With (Hetero)Aryl Boronic Acids for DNA-Encoded Libraries

et al. 2022

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An efficient method for the C-C bond formation via water soluble Na2PdCl4/sSPhos mediated Suzuki-Miyaura cross-coupling reaction of DNA-conjugated aryl iodide with (het)aryl boronic acids has been developed. This reaction proceeds at 37°C in water and acetonitrile (4:1) system. We also demonstrated that numerous aromatic and heteroaromatic boronic acids of different electronic natures, and harboring various functional groups, were highly compatible providing the desired coupling products in good to excellent yields. This DNA-compatible Suzuki-Miyaura cross-coupling reaction has strong potential to construct DNA-Encoded Libraries (DELs) in the context of drug discovery.

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“…DELs are typically less diverse, but there are examples of DELs composed of as many as 10 12 different compounds. 13 The enormous sequence and structure diversities in oligonucleotide libraries along with the availability of adequate screening tools makes such libraries very attractive for in vitro selection of affinity probes and hits in early stage drug discovery. 14,15 Efficient physical partitioning of binders from nonbinders constitutes a major challenge for the field of binder selection from oligonucleotide libraries.…”

mentioning

confidence: 99%

“…There are two major types of oligonucleotide libraries: random-sequence libraries, which are used for the selection of DNA and RNA aptamers, , and DNA-encoded libraries (DELs), which are used for selecting small-molecule ligands. Identifying oligonucleotide sequences of selected aptamers facilitates chemical synthesis of their replicas.…”

mentioning

confidence: 99%

How to Develop and Prove High-Efficiency Selection of Ligands from Oligonucleotide Libraries: A Universal Framework for Aptamers and DNA-Encoded Small-Molecule Ligands

Krylova

Beloborodov

et al. 2021

Anal. Chem.

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Screening molecular libraries for ligands capable of binding proteins is widely used for hit identification in the early drug discovery process. Oligonucleotide libraries provide a very high diversity of compounds, while the combination of the polymerase chain reaction and DNA sequencing allow the identification of ligands in low copy numbers selected from such libraries. Ligand selection from oligonucleotide libraries requires mixing the library with the target followed by the physical separation of the ligand–target complexes from the unbound library. Cumulatively, the low abundance of ligands in the library and the low efficiency of available separation methods necessitate multiple consecutive rounds of partitioning. Multiple rounds of inefficient partitioning make the selection process ineffective and prone to failures. There are continuing efforts to develop a separation method capable of reliably generating a pure pool of ligands in a single round of partitioning; however, none of the proposed methods for single-round selection have been universally adopted. Our analysis revealed that the developers’ efforts are disconnected from each other and hindered by the lack of quantitative criteria of selection quality assessment. Here, we present a formalism that describes single-round selection mathematically and provides parameters for quantitative characterization of selection quality. We use this formalism to define a universal strategy for development and validation of single-round selection methods. Finally, we analyze the existing partitioning methods, the published single-round selection reports, and some pertinent practical considerations through the prism of this formalism. This formalism is not an experimental protocol but a framework for correct development of experimental protocols. While single-round selection is not a goal by itself and may not always suffice selection of good-quality ligands, our work will help developers of highly efficient selection approaches to consolidate their efforts under an umbrella of universal quantitative criteria of method development and assessment.

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Erratum: Design, synthesis and selection of DNA-encoded small-molecule libraries

Abstract: In the version of this article initially published, the IC 50 values in the table in Figure 3c were listed as nM instead of µM. The error has been corrected in the HTML and PDF versions of the article. 772volume 5 number 10 october 2009 nature chemical biology e r r ata

Cited by 9 publications

References 1 publication

Advances in steady-state continuous-flow purification by small-scale free-flow electrophoresis

Advances in steady-state continuous-flow purification by small-scale free-flow electrophoresis

DNA-Compatible Suzuki-Miyaura Cross-Coupling Reaction of Aryl Iodides With (Hetero)Aryl Boronic Acids for DNA-Encoded Libraries

How to Develop and Prove High-Efficiency Selection of Ligands from Oligonucleotide Libraries: A Universal Framework for Aptamers and DNA-Encoded Small-Molecule Ligands

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