Rational Design of Macrocyclic Noncovalent Inhibitors of SARS-CoV-2 Mpro from a DNA-Encoded Chemical Library Screening Hit That Demonstrate Potent Inhibition against Pan-Coronavirus Homologues and Nirmatrelvir-Resistant Variants DOI
Xu Wang, Dimitar Gotchev, Kristi Fan

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(21), P. 19623 - 19667

Published: Oct. 25, 2024

The recent global COVID-19 pandemic has highlighted treatments for coronavirus infection as an unmet medical need. main protease (M

Language: Английский

Photochemical-Promoted Cross-Coupling Reaction of Alkyl Boronate Esters with DNA-Conjugated Aryl Bromides for DNA-Encoded Library Synthesis DOI

Baiyang Mu,

Yiwei Zhang, Xudong Wang

et al.

Bioconjugate Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

The C(sp2)-C(sp3) cross-coupling reaction is an effective way to increase the C(sp3) content in compound collections for drug discovery, enhancing molecular diversity and offering a unique chemistry starting point. In this study, we report mild, DNA-compatible, off-DNA-inert photochemical inspired by amino radical transfer strategy. This method demonstrates broad substrate scopes DNA-encoded library (DEL) constructions, utilizing commonly available structures on DNA diverse alkyl boronate ester building blocks, which have not been widely applied current DEL chemical space.

Language: Английский

Citations

0
Copper-Mediated Three-Component Reaction for the Synthesis of N-Sulfonylamidine on DNA DOI
Taehyun Kwon, Yeonhee Lee, Kyungjin Cho

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

DNA-encoded library (DEL) technology is a transformative tool for identifying bioactive compounds in pharmaceutical research. This study presents an optimized copper-mediated reaction to synthesize N-sulfonylamidine derivatives from DNA-conjugated alkynes and sulfonyl azides under mild conditions. Amines serve as nucleophiles, enabling selective functionalization conditions while preserving DNA integrity. Through systematic refinement of substrate evaluation, the approach demonstrated high tolerance diverse functional groups, significantly expanding DEL-accessible chemical space. The developed DNA-compatible method underscores role DELs enhancing drug discovery by facilitating introduction novel pharmacophores into compound libraries.

Language: Английский

Citations

0
DNA-Compatible Huisgen [3 + 2] Cycloaddition of In Situ Formed Nitrile Oxides with Alkenes or Alkynes to Synthesize Isoxazolines or Isoxazoles DOI
Gaonan Wang,

Xiaona Zhang,

Hui Zhu

et al.

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 13, 2025

DNA-encoded chemical library (DECL) technology is recognized as a robust screening platform for drug discovery. Developing new DNA-compatible reactions crucial expanding the space of DECLs. Cyclization reactions, particularly those involving formation heterocycles, offer unique and efficient methods accessing privileged scaffolds or lead-like small molecules. In this study, we introduce two that utilize readily accessible aldehydes to create substituted isoxazolines isoxazoles by 1,3-dipolar cycloaddition reaction. These demonstrate high conversion efficiency can be applied wide range substrates. The are do not cause significant DNA degradation.

Language: Английский

Citations

0
Drug discovery technologies–Current and future trends DOI

Mark C. Noe,

Claire M. Steppan,

Andrea D. Weston

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Synthesis of Thiohydantoin Scaffolds on DNA for Focused DNA-Encoded Library Construction DOI
Xianfu Fang,

Yunzhu Ju,

Jiayou Wang

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 3, 2024

Thiohydantoin represents a significant class of biologically active privileged heterocyclic scaffolds. Herein, we present convenient and robust DNA-compatible method for constructing thiohydantoin-focused DNA-encoded library. This reaction can be applied to wide variety isothiocyanate partners, arylamine feedstocks, diverse α-amine acid derivatives, exhibiting excellent conversions, high functional group tolerance, preservation DNA tag integrity. Our allows easy access valuable three-cycle

Language: Английский

Citations

3
Mask and Release Strategy‐Enabled Diversity‐Oriented Synthesis for DNA‐Encoded Library DOI Creative Commons
Silin Zhang,

Haiman Zhang,

Xiawen Liu

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 11(6)

Published: Dec. 3, 2023

Abstract An ideal DNA‐encoded library (DEL) selection requires the to consist of diverse core skeletons and cover chemical space as much possible. However, lack efficient on‐DNA synthetic approaches toward has greatly restricted diversity DEL. To mitigate this issue, work disclosed a “Mask & Release” strategy streamline challenging skeleton synthesis. N ‐phenoxyacetamide is used masked phenol versatile directing group mediate diversified DNA‐compatible C‐H functionalization, introducing 1st‐dimensional at defined site, simultaneously releasing functionality, which can facilitate introduction 2nd diversity. This not only provides set syntheses DNA‐conjugated drug‐like such ortho ‐alkenyl/sulfiliminyl/cyclopropyl phenol, benzofuran, dihydrobenzofuran but also paradigm for method development.

Language: Английский

Citations

9
FSO2N3-Mediated On-DNA Diazo-Transfer Chemistry DOI
Qianping Huang,

Yuang Gu,

An Qin

et al.

ACS Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(9), P. 1591 - 1597

Published: Aug. 23, 2024

DNA-encoded library (DEL) is a powerful hit selection technique in both basic science and innovative drug discovery. In this study, we report robust straightforward DNA-compatible diazo-transfer reaction utilizing FSO

Language: Английский

Citations

1
Calcium(II)-Catalyzed off-/on-DNA Reductive Deuteration Amination in HFIP: Modular Access to N-α-Deuterated Amino Acids DOI Creative Commons
Shengdong Wang, Haoran Li,

Yuwei Liu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 27, 2024

Abstract The development of practical and selective deuterium incorporation strategies for building deuterated molecules, especially deuterium-labeled amino acids, has become an increasing focus in basic research, but still remains challenging. We herein report a bioinspired calcium(II)/HFIP-catalyzed site-selective modular reductive deuteration amination simple keto acids/esters with amines by using d2-Hantzsch ester as the source, delivering N-α-deuterated acid motifs remarkable efficiency (>99 ratio) diverse functionality (>130 examples), which various substrates, including peptides, drug molecules natural products bearing different substituted forms, was found to be well compatible. Besides, application this strategy on-DNA synthesis DNA-tagged acids/peptides been exemplified. work provides efficient innovative solution chemistry should have robust potential organic synthesis, medicinal chemical biology.

Language: Английский

Citations

1
LNP-mRNA delivers TNF-α antibody to deep cartilage and protects against osteoarthritis DOI

Baixing Li,

Lei Cui, Keyu Kong

et al.

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 500, P. 156723 - 156723

Published: Oct. 16, 2024

Language: Английский

Citations

1
On-DNA Mannich Reaction for DNA-Encoded Library Synthesis DOI
Danila Ryzhikh, Hyewon Seo, Jihoon Lee

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(22), P. 16957 - 16963

Published: Nov. 1, 2024

The β-amino ketones produced through the Mannich reaction hold significant potential as candidates for various drugs. In this study, we optimized on-DNA conditions and applied them to investigate reactions of DNA-conjugated aldehydes with amine ketone building blocks. developed preserved DNA integrity established viable routes library production. These results underscore in DNA-encoded (DEL) synthesis.

Language: Английский

Citations

1