The impact of ionization states of matrix metalloproteinase inhibitors on docking-based inhibitor design

Haizhen Andrew Zhong, Melissa A. Wees, Theresa D. Faure, Carol Carrillo, Jack Arbiser, J. Phillip Bowen

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The influence of ionization states of hydroxamates and retrohydroxamates and the presence of zinc ions in the active site were investigated using the wild-type and E402Q mutant of MMP-9. The deprotonated hydroxamates showed a significantly enhanced enrichment factor in the presence of zinc ions. A pharmacophore model was developed based on the deprotonated compounds and was used to identify four structurally diverse compounds with antiproliferative activities.

Original languageEnglish (US)
Pages (from-to)455-460
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume2
Issue number6
DOIs
StatePublished - Jun 9 2011

Fingerprint

Matrix Metalloproteinase Inhibitors
Ionization
Zinc
Ions
Matrix Metalloproteinases
Catalytic Domain

Keywords

  • Protonation state
  • and zinc binding group
  • chalcone
  • curcumin

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

The impact of ionization states of matrix metalloproteinase inhibitors on docking-based inhibitor design. / Zhong, Haizhen Andrew; Wees, Melissa A.; Faure, Theresa D.; Carrillo, Carol; Arbiser, Jack; Bowen, J. Phillip.

In: ACS Medicinal Chemistry Letters, Vol. 2, No. 6, 09.06.2011, p. 455-460.

Research output: Contribution to journalArticle

Zhong, Haizhen Andrew ; Wees, Melissa A. ; Faure, Theresa D. ; Carrillo, Carol ; Arbiser, Jack ; Bowen, J. Phillip. / The impact of ionization states of matrix metalloproteinase inhibitors on docking-based inhibitor design. In: ACS Medicinal Chemistry Letters. 2011 ; Vol. 2, No. 6. pp. 455-460.
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