A Handbook for DNA‐Encoded Chemistry

doi:10.1002/9781118832738

Cited by 49 publications

(3 citation statements)

References 33 publications

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“…The synthesized building blocks serve as promising precursors for creating a diverse set of o- benzene analogues with potential biological activity. Furthermore, they can serve as compact, structurally rigid core building blocks suitable for both conventional combinatorial and DNA-encoded chemistry approaches.…”

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confidence: 99%

Stellane at the Forefront: Derivatization and Reactivity Studies of a Promising Saturated Bioisostere of ortho-Substituted Benzenes

Smyrnov,

Melnykov,

Pashenko

et al. 2024

Org. Lett.

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This work highlights stellane's cage stability and derivatization opportunities. A diverse range of building blocks were synthesized using modern synthesis protocols to demonstrate stellane's reactivity and chemical tolerance across different reaction systems, proving its promise as a bioisosteric scaffold. It can be utilized in scaffold-based molecular design and is superior in terms of topological precision compared to existing ortho isosteres, as well as monosubstituted benzene mimetics, holding the potential to become a robust platform for future medicinal chemistry studies.

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confidence: 99%

Stellane at the Forefront: Derivatization and Reactivity Studies of a Promising Saturated Bioisostere of ortho-Substituted Benzenes

Smyrnov,

Melnykov,

Pashenko

et al. 2024

Org. Lett.

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“…On the basis of the handbook of DEL, traditional methods, such as Fischer indole synthesis, applying high temperatures and strongly acidic or inert conditions, are either not feasible on-DNA or propose detrimental reaction conditions to DNA. , Recently, Kazmierski et al reported potent IDO1 inhibitors identified by indole-based DEL screening (Scheme a) . Although the strategy of applying Larock indole synthesis has been revealed, no experimental details were disclosed.…”

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confidence: 99%

On-DNA Synthesis of Multisubstituted Indoles

Németh,

Kollár,

Németh

et al. 2023

Org. Lett.

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The increasing role of the DNA-encoded library technology in early phase drug discovery represents a significant demand for DNA-compatible synthetic methods for therapeutically relevant heterocycles. Herein, we report the first on-DNA synthesis of multisubstituted indoles via a cascade reaction of Sonogashira coupling and intramolecular ring closure. Further functionalization by Suzuki coupling at the third position exploits a diverse chemical space. The high fidelity of the method also enabled the construction of an indole-based mock library.

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“…Several analytical methods have been utilized to characterize the conversions of the on-DNA chemical reactions and enzymatic ligation reactions in DECL synthesis (Figure ). In the initial stage before pooling, all on-DNA transformations may be directly monitored by liquid chromatography–mass spectrometry (LC-MS); however after pooling, individual species with similar length DNA tags typically cannot be separated, and spectra are complex. Although the large mass shift caused by the ligation of DNA segments still enables direct assessment by mass spectrometry, DNA ligations are also commonly monitored by agarose or polyacrylamide gel electrophoresis.…”

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confidence: 99%

Cholesterol-Modified Oligonucleotides as Internal Reaction Controls during DNA-Encoded Chemical Library Synthesis

Yang¹,

He²,

Zhu³

et al. 2021

Bioconjugate Chem.

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We report two cholesterol-modified oligonucleotides for use as internal controls for on-DNA reactions during the pooled stages of a DNA-encoded chemical library (DECL) synthesis. As these cholesterol-tagged oligonucleotides are chromatographically separable from normal DECL intermediates, they can be directly monitored by mass spectrometry to track reaction progression within a complex pool of DNA. We observed similar product conversions for reactions on substrates linked to a standard DECL DNA headpiece, to the cholesterol-modified oligonucleotides, and to the cholesterol-modified oligonucleotides while in the presence of pooled DECL synthetic intermediatesvalidating their use as a representative control. We also highlight an example from a DECL production in which the use of the cholesterol-modified oligonucleotides provided quality control information that guided synthetic decisions. We conclude that the use of cholesterol-modified oligonucleotides as a regular control will significantly improve the quality of DECL productions.

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A Handbook for DNA‐Encoded Chemistry

Cited by 49 publications

References 33 publications

Stellane at the Forefront: Derivatization and Reactivity Studies of a Promising Saturated Bioisostere of ortho-Substituted Benzenes

Stellane at the Forefront: Derivatization and Reactivity Studies of a Promising Saturated Bioisostere of ortho-Substituted Benzenes

On-DNA Synthesis of Multisubstituted Indoles

Cholesterol-Modified Oligonucleotides as Internal Reaction Controls during DNA-Encoded Chemical Library Synthesis

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