Druggability Assessment of Targets Used in Kinetic Target-Guided Synthesis

M. Yagiz Unver, Robin M. Gierse, Harry Ritchie, Anna K. H. Hirsch*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)

Abstract

Kinetic target-guided synthesis (KTGS) is a powerful strategy in which the biological target selects its own inhibitors by assembling them from biocompatible reagents via an irreversible process. In this approach, the biological target accelerates the reaction between complementary building blocks by bringing them in close proximity and proper orientation. KTGS has found application on various targets. Herein, we performed a druggability assessment for each target family reported in KTGS, calculated the pocket properties, and used them to extract possible discriminating factors for successful KTGS studies. A trend for less enclosed pockets emerged, but overall we conclude that the KTGS approach is universal and could be used without restrictions regarding the physicochemical properties of the addressed pocket.

Original languageEnglish
Pages (from-to)9395-9409
Number of pages15
JournalJournal of Medicinal Chemistry
Volume61
Issue number21
DOIs
Publication statusPublished - 8-Nov-2018

Keywords

  • SITU CLICK CHEMISTRY
  • DYNAMIC COMBINATORIAL CHEMISTRY
  • IN-SITU
  • DRUG DISCOVERY
  • MOLECULAR RECOGNITION
  • HIV-1 PROTEASE
  • BINDING-SITE
  • INHIBITORS
  • ENZYME
  • ACETYLCHOLINESTERASE

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