title: A peptide antagonist of the TLR4-MD2 interaction.
abstract: Toll-like receptors are an integral part of innate immunity in the central nervous system (CNS); they orchestrate a robust defense in response to both exogenous and endogenous danger signals. Recently, toll-like receptor 4 (TLR4) has emerged as a therapeutic target for the treatment of CNS-related diseases such as sepsis and chronic pain. We herein report a chemical biology approach by using a rationally designed peptide inhibitor to disrupt the TLR4-MD2 association, thereby blocking TLR4 signaling.
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215, USA.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Slivka
authors.forename: Mitesh
authors.initials: M
authors.lastname: Shridhar
authors.forename: Gui-in
authors.initials: GI
authors.lastname: Lee
authors.forename: Deanne W
authors.initials: DW
authors.lastname: Sammond
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hutchinson
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Martinko
authors.forename: Madison M
authors.initials: MM
authors.lastname: Buchanan
authors.forename: Page W
authors.initials: PW
authors.lastname: Sholar
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Kearney
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Harrison
authors.forename: Linda R
authors.initials: LR
authors.lastname: Watkins
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D019295:Computational Biology; D051218:Lymphocyte Antigen 96; D051379:Mice; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D010455:Peptides; D051197:Toll-Like Receptor 4