Discovery of a new class of non-β-lactam inhibitors of penicillin-binding proteins with gram-positive antibacterial activity

Peter I. O'Daniel; Zhihong Peng; Hualiang Pi; Sebastian A. Testero; Derong Ding; Edward Spink; Erika Leemans; Marc A. Boudreau; Takao Yamaguchi; Valerie A. Schroeder; William R. Wolter; Leticia I. Llarrull; Wei Song; Elena Lastochkin; Malika Kumarasiri; Nuno T. Antunes; Mana Espahbodi; Katerina Lichtenwalter; Mark A. Suckow; Sergei Vakulenko; Shahriar Mobashery; Mayland Chang

doi:10.1021/ja500053x

Discovery of a new class of non-β-lactam inhibitors of penicillin-binding proteins with gram-positive antibacterial activity

Peter I. O'Daniel
, Zhihong Peng
, Hualiang Pi
, Sebastian A. Testero
, Derong Ding
, Edward Spink
, Erika Leemans
, Marc A. Boudreau
, Takao Yamaguchi
, Valerie A. Schroeder
, William R. Wolter
, Leticia I. Llarrull
, Wei Song
, Elena Lastochkin
, Malika Kumarasiri
, Nuno T. Antunes
, Mana Espahbodi
, Katerina Lichtenwalter
, Mark A. Suckow
, Sergei Vakulenko

Shahriar Mobashery, Mayland Chang

Biomedical Engineering

Producción científica: Article › revisión exhaustiva

130 Citas (Scopus)

Resumen

Infections caused by hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA) are a serious global public-health concern, as MRSA has become broadly resistant to many classes of antibiotics. We disclose herein the discovery of a new class of non-β-lactam antibiotics, the oxadiazoles, which inhibit penicillin-binding protein 2a (PBP2a) of MRSA. The oxadiazoles show bactericidal activity against vancomycin-and linezolid-resistant MRSA and other Gram-positive bacterial strains, in vivo efficacy in a mouse model of infection, and have 100% oral bioavailability.

Idioma original	English
Páginas (desde-hasta)	3664-3672
Número de páginas	9
Publicación	Journal of the American Chemical Society
Volumen	136
N.º	9
DOI	https://doi.org/10.1021/ja500053x
Estado	Published - mar 5 2014

Financiación

Financiadores

Número del financiador

National Institutes of Health (NIH)

AI090818

National Institute of Allergy and Infectious F32-AI286447 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI168214 Jason W. Rosch Diseases National Institute of Allergy and Infectious P30 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R00-AI166116 Christopher D. Radka Diseases National Institute of Allergy and Infectious T32-AI106700 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI192221 Jason W. Rosch Diseases National Inst...

R01AI090818

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

Catalysis
Biochemistry
General Chemistry
Colloid and Surface Chemistry

Acceder al documento

10.1021/ja500053x

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Link to publication in Scopus

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O'Daniel, P. I., Peng, Z., Pi, H., Testero, S. A., Ding, D., Spink, E., Leemans, E., Boudreau, M. A., Yamaguchi, T., Schroeder, V. A., Wolter, W. R., Llarrull, L. I., Song, W., Lastochkin, E., Kumarasiri, M., Antunes, N. T., Espahbodi, M., Lichtenwalter, K., Suckow, M. A., ... Chang, M. (2014). Discovery of a new class of non-β-lactam inhibitors of penicillin-binding proteins with gram-positive antibacterial activity. Journal of the American Chemical Society, 136(9), 3664-3672. https://doi.org/10.1021/ja500053x

@article{d88085d155aa4640b786ec20b2617eef,

title = "Discovery of a new class of non-β-lactam inhibitors of penicillin-binding proteins with gram-positive antibacterial activity",

abstract = "Infections caused by hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA) are a serious global public-health concern, as MRSA has become broadly resistant to many classes of antibiotics. We disclose herein the discovery of a new class of non-β-lactam antibiotics, the oxadiazoles, which inhibit penicillin-binding protein 2a (PBP2a) of MRSA. The oxadiazoles show bactericidal activity against vancomycin-and linezolid-resistant MRSA and other Gram-positive bacterial strains, in vivo efficacy in a mouse model of infection, and have 100\% oral bioavailability.",

author = "O'Daniel, \{Peter I.\} and Zhihong Peng and Hualiang Pi and Testero, \{Sebastian A.\} and Derong Ding and Edward Spink and Erika Leemans and Boudreau, \{Marc A.\} and Takao Yamaguchi and Schroeder, \{Valerie A.\} and Wolter, \{William R.\} and Llarrull, \{Leticia I.\} and Wei Song and Elena Lastochkin and Malika Kumarasiri and Antunes, \{Nuno T.\} and Mana Espahbodi and Katerina Lichtenwalter and Suckow, \{Mark A.\} and Sergei Vakulenko and Shahriar Mobashery and Mayland Chang",

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doi = "10.1021/ja500053x",

language = "English",

volume = "136",

pages = "3664--3672",

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O'Daniel, PI, Peng, Z, Pi, H, Testero, SA, Ding, D, Spink, E, Leemans, E, Boudreau, MA, Yamaguchi, T, Schroeder, VA, Wolter, WR, Llarrull, LI, Song, W, Lastochkin, E, Kumarasiri, M, Antunes, NT, Espahbodi, M, Lichtenwalter, K, Suckow, MA, Vakulenko, S, Mobashery, S & Chang, M 2014, 'Discovery of a new class of non-β-lactam inhibitors of penicillin-binding proteins with gram-positive antibacterial activity', Journal of the American Chemical Society, vol. 136, n.º 9, pp. 3664-3672. https://doi.org/10.1021/ja500053x

TY - JOUR

T1 - Discovery of a new class of non-β-lactam inhibitors of penicillin-binding proteins with gram-positive antibacterial activity

AU - O'Daniel, Peter I.

AU - Peng, Zhihong

AU - Pi, Hualiang

AU - Testero, Sebastian A.

AU - Ding, Derong

AU - Spink, Edward

AU - Leemans, Erika

AU - Boudreau, Marc A.

AU - Yamaguchi, Takao

AU - Schroeder, Valerie A.

AU - Wolter, William R.

AU - Llarrull, Leticia I.

AU - Song, Wei

AU - Lastochkin, Elena

AU - Kumarasiri, Malika

AU - Antunes, Nuno T.

AU - Espahbodi, Mana

AU - Lichtenwalter, Katerina

AU - Suckow, Mark A.

AU - Vakulenko, Sergei

AU - Mobashery, Shahriar

AU - Chang, Mayland

PY - 2014/3/5

Y1 - 2014/3/5

N2 - Infections caused by hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA) are a serious global public-health concern, as MRSA has become broadly resistant to many classes of antibiotics. We disclose herein the discovery of a new class of non-β-lactam antibiotics, the oxadiazoles, which inhibit penicillin-binding protein 2a (PBP2a) of MRSA. The oxadiazoles show bactericidal activity against vancomycin-and linezolid-resistant MRSA and other Gram-positive bacterial strains, in vivo efficacy in a mouse model of infection, and have 100% oral bioavailability.

AB - Infections caused by hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA) are a serious global public-health concern, as MRSA has become broadly resistant to many classes of antibiotics. We disclose herein the discovery of a new class of non-β-lactam antibiotics, the oxadiazoles, which inhibit penicillin-binding protein 2a (PBP2a) of MRSA. The oxadiazoles show bactericidal activity against vancomycin-and linezolid-resistant MRSA and other Gram-positive bacterial strains, in vivo efficacy in a mouse model of infection, and have 100% oral bioavailability.

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SN - 0002-7863

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EP - 3672

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

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Discovery of a new class of non-β-lactam inhibitors of penicillin-binding proteins with gram-positive antibacterial activity

Resumen

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

Acceder al documento

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