Screening of a Novel Fragment Library with Functional Complexity against Mycobacterium tuberculosis InhA Articles uri icon

authors

  • PRATI, FEDERICA
  • ZUCCOTTO, FABIO
  • FLETCHER, DANIEL
  • CONVERY, MAIRE
  • FERNÁNDEZ MENÉNDEZ, RAQUEL
  • BATES, ROBERT
  • ENCINAS, LOURDES
  • ZENG, JINGKUN
  • CHUNG, CHUN-WA
  • DE DIOS ANTÓN, PACO
  • MENDOZA LOSANA, ALFONSO
  • MACKENZIE, CLAIRE
  • GREEN, SIMON R.
  • HUGGETT, MARGARET
  • BARROS, DAVID
  • WYATT, PAUL G.
  • RAY, PETER C.

publication date

  • February 2018

start page

  • 672

end page

  • 677

issue

  • 7

volume

  • 13

International Standard Serial Number (ISSN)

  • 1860-7179

Electronic International Standard Serial Number (EISSN)

  • 1860-7187

abstract

  • Our findings reported herein provide support for the benefits of including functional group complexity (FGC) within fragments when screening against protein targets such as Mycobacterium tuberculosis InhA. We show that InhA fragment actives with FGC maintained their binding pose during elaboration. Furthermore, weak fragment hits with functional group handles also allowed for facile fragment elaboration to afford novel and potent InhA inhibitors with good ligand efficiency metrics for optimization.

keywords

  • fragment based drug discovery; functional group complexity; inha; tuberculosis