DNA-Encoded Chemical Libraries

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.

Includes cutting-edge methods and protocols Provides step-by-step detail essential for reproducible results Contains key notes and implementation advice from the experts

Inhalt
Library Synthesis: Building Block Selection, Handling, and Tracking.- Library Synthesis: Building Block Validation.- Library Synthesis and Analytics.- Chemical Ligation of Oligonucleotide Tags to Support Encoded Chemical Library Synthesis.- On-DNA Reductive Amination and Alkylation.- On-DNA-1,2,3-Triazole Formation via Click Reaction.- On-DNA Suzuki-Miyaura Cross-Coupling.- On-DNA Pd and Cu Promoted C-N Cross-Coupling Reactions.- Palladium Promoted On-DNA Heck Reactions.- Ruthenium Promoted On-DNA C-H Activation Reaction.- DNA-Compatible Nitro Reduction and Synthesis of Benzimidazoles.- Condensation of DNA-Conjugated Imines with Homophthalic Anhydride for the Synthesis of Isoquinolones On-DNA.- DNA Encoding of Natural Products.- Initiating DNA-Encoded Library Synthesis with a Hexathymidine DNA Oligonucleotide.- One Bead-One Compound (OBOC) Peptidomimetic Encoded Library Synthesis via Split-and-Pool Methods.- DNA Conjugates as Tool Compounds for DEL Selections.- Quantitation of DNA Encoded Libraries by qPCR.- Target Protein Design and Pre-Selection Analysis.- DEL Selections Against a Soluble Protein Target.- Selection Method of DNA-Encoded Chemical Library for Irreversible Covalent Binders.- Next Generation Sequencing of DNA-Encoded Libraries.- Translation of DNA Sequence to Chemical Structure in DNA Encoded Libraries.- Analysis of DNA-Encoded Library Screening Data: Selection of Molecules for Synthesis.- High Throughput Binder Confirmation (HTBC).- High-Throughput Binder Confirmation Using Affinity Selection Mass Spectrometry.