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J Med Chem. 2016 May 26;59(10):4812-30. doi: 10.1021/acs.jmedchem.6b00177. Epub 2016 Apr 25.

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

Author information

1
Department of Chemistry and the Skaggs Institute of Chemical Biology, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
2
Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center , Dallas, Texas 75390, United States.
3
Department of Biophysics, University of Texas Southwestern Medical Center , Dallas, Texas 75390, United States.
4
Department of Genetics, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.

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.

PMID:
27050713
PMCID:
PMC4882283
DOI:
10.1021/acs.jmedchem.6b00177
[Indexed for MEDLINE]
Free PMC Article

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