New Series of BPL Inhibitors To Probe the Ribose-Binding Pocket of Staphylococcus aureus Biotin Protein Ligase

Jiage Feng; Ashleigh S. Paparella; William Tieu; David Heim; Sarah Clark; Andrew Hayes; Grant W. Booker; Steven W. Polyak; Andrew D. Abell

doi:10.1021/acsmedchemlett.6b00248

New Series of BPL Inhibitors To Probe the Ribose-Binding Pocket of Staphylococcus aureus Biotin Protein Ligase

Jiage Feng, Ashleigh S. Paparella, William Tieu, David Heim, Sarah Clark, Andrew Hayes, Grant W. Booker, Steven W. Polyak, Andrew D. Abell

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

13 Citations (Scopus)

Abstract

Replacing the labile adenosinyl-substituted phosphoanhydride of biotinyl-5′-AMP with a N1-benzyl substituted 1,2,3-triazole gave a new truncated series of inhibitors of Staphylococcus aureus biotin protein ligase (SaBPL). The benzyl group presents to the ribose-binding pocket of SaBPL based on in silico docking. Halogenated benzyl derivatives (12t, 12u, 12w, and 12x) proved to be the most potent inhibitors of SaBPL. These derivatives inhibited the growth of S. aureus ATCC49775 and displayed low cytotoxicity against HepG2 cells.

Original language	English
Pages (from-to)	1068-1072
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	7
Issue number	12
DOIs	https://doi.org/10.1021/acsmedchemlett.6b00248
Publication status	Published or Issued - 8 Dec 2016
Externally published	Yes

Keywords

Enzyme inhibitors
Staphylococcus aureus
antibiotics
biotin protein ligase

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1021/acsmedchemlett.6b00248

Cite this

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title = "New Series of BPL Inhibitors To Probe the Ribose-Binding Pocket of Staphylococcus aureus Biotin Protein Ligase",

abstract = "Replacing the labile adenosinyl-substituted phosphoanhydride of biotinyl-5′-AMP with a N1-benzyl substituted 1,2,3-triazole gave a new truncated series of inhibitors of Staphylococcus aureus biotin protein ligase (SaBPL). The benzyl group presents to the ribose-binding pocket of SaBPL based on in silico docking. Halogenated benzyl derivatives (12t, 12u, 12w, and 12x) proved to be the most potent inhibitors of SaBPL. These derivatives inhibited the growth of S. aureus ATCC49775 and displayed low cytotoxicity against HepG2 cells.",

keywords = "Enzyme inhibitors, Staphylococcus aureus, antibiotics, biotin protein ligase",

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doi = "10.1021/acsmedchemlett.6b00248",

language = "English",

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T1 - New Series of BPL Inhibitors To Probe the Ribose-Binding Pocket of Staphylococcus aureus Biotin Protein Ligase

AU - Feng, Jiage

AU - Paparella, Ashleigh S.

AU - Tieu, William

AU - Heim, David

AU - Clark, Sarah

AU - Hayes, Andrew

AU - Booker, Grant W.

AU - Polyak, Steven W.

AU - Abell, Andrew D.

PY - 2016/12/8

Y1 - 2016/12/8

N2 - Replacing the labile adenosinyl-substituted phosphoanhydride of biotinyl-5′-AMP with a N1-benzyl substituted 1,2,3-triazole gave a new truncated series of inhibitors of Staphylococcus aureus biotin protein ligase (SaBPL). The benzyl group presents to the ribose-binding pocket of SaBPL based on in silico docking. Halogenated benzyl derivatives (12t, 12u, 12w, and 12x) proved to be the most potent inhibitors of SaBPL. These derivatives inhibited the growth of S. aureus ATCC49775 and displayed low cytotoxicity against HepG2 cells.

AB - Replacing the labile adenosinyl-substituted phosphoanhydride of biotinyl-5′-AMP with a N1-benzyl substituted 1,2,3-triazole gave a new truncated series of inhibitors of Staphylococcus aureus biotin protein ligase (SaBPL). The benzyl group presents to the ribose-binding pocket of SaBPL based on in silico docking. Halogenated benzyl derivatives (12t, 12u, 12w, and 12x) proved to be the most potent inhibitors of SaBPL. These derivatives inhibited the growth of S. aureus ATCC49775 and displayed low cytotoxicity against HepG2 cells.

KW - Enzyme inhibitors

KW - Staphylococcus aureus

KW - antibiotics

KW - biotin protein ligase

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ER -

New Series of BPL Inhibitors To Probe the Ribose-Binding Pocket of Staphylococcus aureus Biotin Protein Ligase

Abstract

Keywords

ASJC Scopus subject areas

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