Discovery and Structure-Activity Relationships of the Neoseptins: A New Class of Toll-like Receptor-4 (TLR4) Agonists

Matthew D. Morin; Ying Wang; Brian T. Jones; Lijing Su; Murali M.R.P. Surakattula; Michael Berger; Hua Huang; Elliot K. Beutler; Hong Zhang; Bruce Beutler; Dale L. Boger

doi:10.1021/acs.jmedchem.6b00177

Discovery and Structure-Activity Relationships of the Neoseptins: A New Class of Toll-like Receptor-4 (TLR4) Agonists

Matthew D. Morin
, Ying Wang
, Brian T. Jones
, Lijing Su
, Murali M.R.P. Surakattula
, Michael Berger
, Hua Huang
, Elliot K. Beutler
, Hong Zhang^*
, Bruce Beutler
, Dale L. Boger

^*Corresponding author for this work

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

33 Scopus citations

Abstract

Herein, we report studies leading to the discovery of the neoseptins and a comprehensive examination of the structure-activity relationships (SARs) of this new class of small-molecule mouse Toll-like receptor 4 (mTLR4) agonists. The compounds in this class, which emerged from screening an α-helix mimetic library, stimulate the immune response, act by a well-defined mechanism (mouse TLR4 agonist), are easy to produce and structurally manipulate, exhibit exquisite SARs, are nontoxic, and elicit improved and qualitatively different responses compared to lipopolysaccharide, even though they share the same receptor.

Original language	English
Pages (from-to)	4812-4830
Number of pages	19
Journal	Journal of Medicinal Chemistry
Volume	59
Issue number	10
DOIs	https://doi.org/10.1021/acs.jmedchem.6b00177
State	Published - 26 May 2016
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2016 American Chemical Society.

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10.1021/acs.jmedchem.6b00177

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Morin, M. D., Wang, Y., Jones, B. T., Su, L., Surakattula, M. M. R. P., Berger, M., Huang, H., Beutler, E. K., Zhang, H., Beutler, B., & Boger, D. L. (2016). Discovery and Structure-Activity Relationships of the Neoseptins: A New Class of Toll-like Receptor-4 (TLR4) Agonists. Journal of Medicinal Chemistry, 59(10), 4812-4830. https://doi.org/10.1021/acs.jmedchem.6b00177

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abstract = "Herein, we report studies leading to the discovery of the neoseptins and a comprehensive examination of the structure-activity relationships (SARs) of this new class of small-molecule mouse Toll-like receptor 4 (mTLR4) agonists. The compounds in this class, which emerged from screening an α-helix mimetic library, stimulate the immune response, act by a well-defined mechanism (mouse TLR4 agonist), are easy to produce and structurally manipulate, exhibit exquisite SARs, are nontoxic, and elicit improved and qualitatively different responses compared to lipopolysaccharide, even though they share the same receptor.",

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AU - Berger, Michael

AU - Huang, Hua

AU - Beutler, Elliot K.

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Discovery and Structure-Activity Relationships of the Neoseptins: A New Class of Toll-like Receptor-4 (TLR4) Agonists

Abstract

Bibliographical note

UN SDGs

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