DNA-Encoded Chemical Libraries: Methods and Protocols

ISBN-13: 9781071625446 / Angielski / Twarda / 2022

Israel, David

Opis

This volume discusses protocols that cover synthesis, screening by selection, and analysis of DNA-encoded chemical libraries (DEL). Chapters in this book focus on methods used to practice DEL technology and include solution phase library synthesis using a variety of chemistries; DNA encoding of chemical structure; design, preparation and analysis of target proteins and tool compounds; screening of soluble protein targets by affinity selection; DEL qPCR, preparative PCR and DNA sequence analysis; computational methods used to analyze selections and choose compounds for resynthesis; and analysis of hit compounds. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls.

Cutting-edge and comprehensive, DNA-Encoded Chemical Libraries: Methods and Protocols is a valuable resource for scientists interested in DEL technology for drug discovery, and will contribute to the continued advancement in this important field.

Spis treści

Preface…
Table of Contents…
Contributing Authors…

1. Library Synthesis: Building Block Selection, Handling, and Tracking
Katelyn J. Billings and Melissa C. Grenier-Davies

2. Library Synthesis: Building Block Validation
Melissa C. Grenier-Davies

3. Library Synthesis and Analytics
Jing Chai

4. Chemical Ligation of Oligonucleotide Tags to Support Encoded Chemical Library Synthesis
Alexander Litovchick and Anthony D. Keefe

5. On-DNA Reductive Amination and Alkylation
Jing Chai

6. On-DNA-1,2,3-Triazole Formation via Click Reaction
Sarah K. Scott

7. On-DNA Suzuki-Miyaura Cross-Coupling
Yun Ding

8. On-DNA Pd and Cu Promoted C-N Cross-Coupling Reactions
Xiaojie Lu and Xuan Wang

9. Palladium Promoted On-DNA Heck Reactions
Xuan Wang and Xiaojie Lu

10. Ruthenium Promoted On-DNA C-H Activation Reaction
Xuan Wang and Xiaojie Lu

11. DNA-Compatible Nitro Reduction and Synthesis of Benzimidazoles
Huang-Chi Du, Ying-Chu Chen, and Hongbing Huang

12. Condensation of DNA-Conjugated Imines with Homophthalic Anhydride for the Synthesis of Isoquinolones On-DNA
Josephine Yuen, Jing Chai, and Yun Ding

13. DNA Encoding of Natural Products
Hongtao Xu and Peixiang Ma

14. Initiating DNA-Encoded Library Synthesis with a Hexathymidine DNA Oligonucleotide
Mateja Klika Škopić, Denise dos Santos Smith, Anne Gohla, Verena B. K. Kunig, and Andreas Brunschweiger

15. One Bead-One Compound (OBOC) Peptidomimetic Encoded Library Synthesis via Split-and-Pool Methods
Claudio Aquino and Mohosin Sarkar

16. DNA Conjugates as Tool Compounds for DEL Selections
David I. Israel

17. Quantitation of DNA Encoded Libraries by qPCR
Christopher S. Kollmann

18. Target Protein Design and Pre-Selection Analysis
Qiuxia Chen and David I. Israel

19. DEL Selections Against a Soluble Protein Target
Qiuxia Chen and Junyang Zhu

20. Selection Method of DNA-Encoded Chemical Library for Irreversible Covalent Binders
Zhengrong Zhu

21. Next Generation Sequencing of DNA-Encoded Libraries
Jian Liu and You Li

22. Translation of DNA Sequence to Chemical Structure in DNA Encoded Libraries
You Li

23. Analysis of DNA-Encoded Library Screening Data: Selection of Molecules for Synthesis
Alexander L. Satz and Weiren Cui

24. High Throughput Binder Confirmation (HTBC)
Bing Xia and Jennifer D. Summerfield

25. High-Throughput Binder Confirmation Using Affinity Selection Mass Spectrometry
Eric X. Shi

Subject Index List…