Fragment-based Lead Discovery and Optimization Using X-Ray Crystallography, Computational Chemistry, and High-throughput Organic Synthesis

Jeff Blaney, Vicki Nienaber, Stephen K. Burley

Research output: Chapter in Book/Report/Conference proceedingChapter

40 Scopus citations

Abstract

This chapter contains sections titled: Introduction Overview of the SGX Structure-driven Fragment-based Lead Discovery Process Fragment Library Design for Crystallographic Screening Considerations for Selecting Fragments SGX Fragment Screening Library Selection Criteria SGX Fragment Screening Library Properties SGX Fragment Screening Library Diversity: Theoretical and Experimental Analyses Crystallographic Screening of the SGX Fragment Library Overview of Crystallographic Screening Obtaining the Initial Target Protein Structure Enabling Targets for Crystallographic Screening Fragment Library Screening at SGX-CAT Analysis of Fragment Screening Results Factor VIIa Case Study of SGX Fragment Library Screening Complementary Biochemical Screening of the SGX Fragment Library Importance of Combining Crystallographic and Biochemical Fragment Screening Selecting Fragments Hits for Chemical Elaboration Fragment Optimization Spleen Tyrosine Kinase Case Study Fragment Optimization Overview Linear Library Optimization Combinatorial Library Optimization Discussion and Conclusions Postscript: SGX Oncology Lead Generation Program References

Original languageEnglish (US)
Title of host publicationFragment-based Approaches in Drug Discovery
PublisherWiley-Blackwell
Pages215-248
Number of pages34
Volume34
ISBN (Electronic)9783527608768
ISBN (Print)3527312919, 9783527312917
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)

Keywords

  • Combining crystallographic and biochemical fragment screening
  • Complementary biochemical screening of the SGX fragment library
  • Computational chemistry
  • Crystallographic screening
  • Drug discovery
  • Experimental applications
  • Experimental techniques
  • Fragment library design
  • Fragment optimization using X-ray crystallography
  • Fragment-based lead discovery
  • High-throughput organic synthesis
  • SGX structure-driven fragment-based lead discovery process

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