Heterocyclic acyl-phosphate bioisostere-based inhibitors of Staphylococcus aureus biotin protein ligase

William Tieu; Angie M. Jarrad; Ashleigh S. Paparella; Kelly A. Keeling; Tatiana P. Soares Da Costa; John C. Wallace; Grant W. Booker; Steven W. Polyak; Andrew D. Abell

doi:10.1016/j.bmcl.2014.08.030

Heterocyclic acyl-phosphate bioisostere-based inhibitors of Staphylococcus aureus biotin protein ligase

William Tieu, Angie M. Jarrad, Ashleigh S. Paparella, Kelly A. Keeling, Tatiana P. Soares Da Costa, John C. Wallace, Grant W. Booker, Steven W. Polyak, Andrew D. Abell

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

19 Scopus citations

Abstract

Inhibitors of Staphylococcus aureus biotin protein ligase (SaBPL) are generated by replacing the acyl phosphate group of biotinyl-5′-AMP with either a 1,2,3-triazole (see 5/10a/10b) or a 1,2,4-oxadiazole (see 7) bioisostere. Importantly, the inhibitors are inactive against the human BPL. The nature of the 5-substituent in the component benzoxazolone of the optimum 1,2,3-triazole series is critical to activity, where this group binds in the ATP binding pocket of the enzyme.

Original language	English (US)
Pages (from-to)	4689-4693
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	19
DOIs	https://doi.org/10.1016/j.bmcl.2014.08.030
State	Published - Oct 1 2014
Externally published	Yes

Keywords

Antibiotics
Bioisosteres
Drug design
Inhibitors
Ligases

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2014.08.030

Cite this

@article{117c97a183b54e209efd9d7fb8e89d96,

title = "Heterocyclic acyl-phosphate bioisostere-based inhibitors of Staphylococcus aureus biotin protein ligase",

abstract = "Inhibitors of Staphylococcus aureus biotin protein ligase (SaBPL) are generated by replacing the acyl phosphate group of biotinyl-5′-AMP with either a 1,2,3-triazole (see 5/10a/10b) or a 1,2,4-oxadiazole (see 7) bioisostere. Importantly, the inhibitors are inactive against the human BPL. The nature of the 5-substituent in the component benzoxazolone of the optimum 1,2,3-triazole series is critical to activity, where this group binds in the ATP binding pocket of the enzyme.",

keywords = "Antibiotics, Bioisosteres, Drug design, Inhibitors, Ligases",

author = "William Tieu and Jarrad, {Angie M.} and Paparella, {Ashleigh S.} and Keeling, {Kelly A.} and {Soares Da Costa}, {Tatiana P.} and Wallace, {John C.} and Booker, {Grant W.} and Polyak, {Steven W.} and Abell, {Andrew D.}",

year = "2014",

month = oct,

day = "1",

doi = "10.1016/j.bmcl.2014.08.030",

language = "English (US)",

volume = "24",

pages = "4689--4693",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "19",

}

TY - JOUR

T1 - Heterocyclic acyl-phosphate bioisostere-based inhibitors of Staphylococcus aureus biotin protein ligase

AU - Tieu, William

AU - Jarrad, Angie M.

AU - Paparella, Ashleigh S.

AU - Keeling, Kelly A.

AU - Soares Da Costa, Tatiana P.

AU - Wallace, John C.

AU - Booker, Grant W.

AU - Polyak, Steven W.

AU - Abell, Andrew D.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Inhibitors of Staphylococcus aureus biotin protein ligase (SaBPL) are generated by replacing the acyl phosphate group of biotinyl-5′-AMP with either a 1,2,3-triazole (see 5/10a/10b) or a 1,2,4-oxadiazole (see 7) bioisostere. Importantly, the inhibitors are inactive against the human BPL. The nature of the 5-substituent in the component benzoxazolone of the optimum 1,2,3-triazole series is critical to activity, where this group binds in the ATP binding pocket of the enzyme.

AB - Inhibitors of Staphylococcus aureus biotin protein ligase (SaBPL) are generated by replacing the acyl phosphate group of biotinyl-5′-AMP with either a 1,2,3-triazole (see 5/10a/10b) or a 1,2,4-oxadiazole (see 7) bioisostere. Importantly, the inhibitors are inactive against the human BPL. The nature of the 5-substituent in the component benzoxazolone of the optimum 1,2,3-triazole series is critical to activity, where this group binds in the ATP binding pocket of the enzyme.

KW - Antibiotics

KW - Bioisosteres

KW - Drug design

KW - Inhibitors

KW - Ligases

UR - http://www.scopus.com/inward/record.url?scp=84907199232&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907199232&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2014.08.030

DO - 10.1016/j.bmcl.2014.08.030

M3 - Article

C2 - 25193234

AN - SCOPUS:84907199232

SN - 0960-894X

VL - 24

SP - 4689

EP - 4693

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 19

ER -

Heterocyclic acyl-phosphate bioisostere-based inhibitors of Staphylococcus aureus biotin protein ligase

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this