A Handbook for DNA-Encoded Chemistry (eBook)

ROBERT A. GOODNOW, JR. is the Executive Director of the Chemistry Innovation Centre, Discovery Sciences at AstraZeneca and the Founder of GoodChem Consulting, LLC. He has extensive experience in drug discovery and chemistry technologies including carbohydrate, combinatorial, oligonucleotide, and analytical chemistry. Robert Goodnow has authored or coauthored nearly 100 publications and patents and has spoken extensively on the topics of drug lead finding and the outsourcing of drug discovery chemistry. He has lectured as an adjunct professor of medicinal chemistry.

Preface vii

Acknowledgments ix

Introductory Comments xi

Contributors xxiii

1 Just enough knowledge... 1
Agnieszka Kowalczyk

2 A brief history of the development of combinatorial chemistry and the emerging need for DNA-encoded chemistry 19
Robert A. Goodnow, Jr.

3 A brief history of DNA-encoded chemistry 45
Anthony D. Keefe

4 DNA-Compatible Chemistry 67
Kin-Chun Luk and Alexander Lee Satz

5 Foundations of a DNA-encoded library (DEL) 99
Alexander Lee Satz

6 Exercises in the Synthesis of DNA-encoded Libraries 123
Steffen P. Creaser and Raksha A. Acharya

7 The DNA Tag: A Chemical gene designed for DNA-encoded libraries 153
Andrew W. Fraley

8 Analytical challenges for DNA-encoded library systems 171
George L. Perkins and G. John Langley

9 Informatics: Functionality and architecture for DNA-encoded library production and screening 201
John A. Feinberg and Zhengwei Peng

10 Theoretical considerations of the application of DNA-encoded libraries to drug discovery 213
Charles Wartchow

11 Begin with the End in Mind: The hit-to-lead process 231
John Proudfoot

12 Enumeration and Visualization of Large Combinatorial Chemical Libraries 247
Sung-Sau So

13 Screening Large Compound Collections 281
Stephen P. Hale

14 Reported applications of DNA-encoded library chemistry 319
Johannes Ottl

15 Dual-Pharmacophore DNA-encoded Chemical Libraries 349
Jörg Scheuermann and Dario Neri

16 Hit Identification and Hit Follow-up 357
Yixin Zhang

17 Using DNA to Program Chemical Synthesis, Discover New Reactions, and Detect Ligand Binding 377
Lynn M. McGregor and David R. Liu

18 The changing feasibility and economics of chemical diversity exploration with DNA-encoded combinatorial approaches 417
Robert A. Goodnow, Jr.

19 Keeping the promise? An outlook on DNA chemical library technology 427
Samu Melkko and Johannes Ottl

Index 435