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

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

doi:10.1021/ml200031m

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

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

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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 language	English (US)
Pages (from-to)	455-460
Number of pages	6
Journal	ACS Medicinal Chemistry Letters
Volume	2
Issue number	6
DOIs	https://doi.org/10.1021/ml200031m
State	Published - Jun 9 2011

Keywords

Protonation state
and zinc binding group
chalcone
curcumin

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1021/ml200031m

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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.",

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AU - Zhong, Haizhen

AU - Wees, Melissa A.

AU - Faure, Theresa D.

AU - Carrillo, Carol

AU - Arbiser, Jack

AU - Bowen, J. Phillip

PY - 2011/6/9

Y1 - 2011/6/9

N2 - 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.

AB - 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.

KW - Protonation state

KW - and zinc binding group

KW - chalcone

KW - curcumin

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

Abstract

Keywords

ASJC Scopus subject areas

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