Development of a triclosan scaffold which allows for adaptations on both the A- and B-ring for transport peptides

Stephen P. Muench; Jozef Stec; Ying Zhou; Gustavo A. Afanador; Martin J. McPhillie; Mark R. Hickman; Patty J. Lee; Susan E. Leed; Jennifer M. Auschwitz; Sean T. Prigge; David W. Rice; Rima McLeod

doi:10.1016/j.bmcl.2013.04.035

Development of a triclosan scaffold which allows for adaptations on both the A- and B-ring for transport peptides

Stephen P. Muench, Jozef Stec, Ying Zhou, Gustavo A. Afanador, Martin J. McPhillie, Mark R. Hickman, Patty J. Lee, Susan E. Leed, Jennifer M. Auschwitz, Sean T. Prigge, David W. Rice, Rima McLeod

Bloomberg School of Public Health

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

10 Scopus citations

Abstract

The enoyl acyl-carrier protein reductase (ENR) enzyme is harbored within the apicoplast of apicomplexan parasites providing a significant challenge for drug delivery, which may be overcome through the addition of transductive peptides, which facilitates crossing the apicoplast membranes. The binding site of triclosan, a potent ENR inhibitor, is occluded from the solvent making the attachment of these linkers challenging. Herein, we have produced 3 new triclosan analogs with bulky A- and B-ring motifs, which protrude into the solvent allowing for the future attachment of molecular transporters for delivery.

Original language	English (US)
Pages (from-to)	3551-3555
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	12
DOIs	https://doi.org/10.1016/j.bmcl.2013.04.035
State	Published - Jun 15 2013

Keywords

Enoyl reductase Triclosan Toxoplasma Plasmodium

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2013.04.035

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Muench, S. P., Stec, J., Zhou, Y., Afanador, G. A., McPhillie, M. J., Hickman, M. R., Lee, P. J., Leed, S. E., Auschwitz, J. M., Prigge, S. T., Rice, D. W., & McLeod, R. (2013). Development of a triclosan scaffold which allows for adaptations on both the A- and B-ring for transport peptides. Bioorganic and Medicinal Chemistry Letters, 23(12), 3551-3555. https://doi.org/10.1016/j.bmcl.2013.04.035

Muench, SP, Stec, J, Zhou, Y, Afanador, GA, McPhillie, MJ, Hickman, MR, Lee, PJ, Leed, SE, Auschwitz, JM, Prigge, ST, Rice, DW & McLeod, R 2013, 'Development of a triclosan scaffold which allows for adaptations on both the A- and B-ring for transport peptides', Bioorganic and Medicinal Chemistry Letters, vol. 23, no. 12, pp. 3551-3555. https://doi.org/10.1016/j.bmcl.2013.04.035

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abstract = "The enoyl acyl-carrier protein reductase (ENR) enzyme is harbored within the apicoplast of apicomplexan parasites providing a significant challenge for drug delivery, which may be overcome through the addition of transductive peptides, which facilitates crossing the apicoplast membranes. The binding site of triclosan, a potent ENR inhibitor, is occluded from the solvent making the attachment of these linkers challenging. Herein, we have produced 3 new triclosan analogs with bulky A- and B-ring motifs, which protrude into the solvent allowing for the future attachment of molecular transporters for delivery.",

keywords = "Enoyl reductase Triclosan Toxoplasma Plasmodium",

author = "Muench, {Stephen P.} and Jozef Stec and Ying Zhou and Afanador, {Gustavo A.} and McPhillie, {Martin J.} and Hickman, {Mark R.} and Lee, {Patty J.} and Leed, {Susan E.} and Auschwitz, {Jennifer M.} and Prigge, {Sean T.} and Rice, {David W.} and Rima McLeod",

note = "Funding Information: We thank Dr. Alan Kozikowski for his contributions. The authors are grateful for the financial support provided by NIAID U01 AI082180 -01 and the Rooney-Alden, Taub, Engel, Pritzker, Harris, Kapnick, Mussilami and Samuel families and the Mann-Cornwell Family Foundation. SPM is supported by an MRC Career Development fellowship (G1000567). ",

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doi = "10.1016/j.bmcl.2013.04.035",

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AU - Muench, Stephen P.

AU - Stec, Jozef

AU - Zhou, Ying

AU - Afanador, Gustavo A.

AU - McPhillie, Martin J.

AU - Hickman, Mark R.

AU - Lee, Patty J.

AU - Leed, Susan E.

AU - Auschwitz, Jennifer M.

AU - Prigge, Sean T.

AU - Rice, David W.

AU - McLeod, Rima

N1 - Funding Information: We thank Dr. Alan Kozikowski for his contributions. The authors are grateful for the financial support provided by NIAID U01 AI082180 -01 and the Rooney-Alden, Taub, Engel, Pritzker, Harris, Kapnick, Mussilami and Samuel families and the Mann-Cornwell Family Foundation. SPM is supported by an MRC Career Development fellowship (G1000567).

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Y1 - 2013/6/15

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Development of a triclosan scaffold which allows for adaptations on both the A- and B-ring for transport peptides

Abstract

Keywords

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