A peptide antagonist of the TLR4-MD2 interaction.
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.
Slivka
Peter F
PF
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215, USA.
Shridhar
Mitesh
M
Lee
Gui-in
GI
Sammond
Deanne W
DW
Hutchinson
Mark R
MR
Martinko
Alexander J
AJ
Buchanan
Madison M
MM
Sholar
Page W
PW
Kearney
Jeffrey J
JJ
Harrison
Jacqueline A
JA
Watkins
Linda R
LR
Yin
Hang
H
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*
D048868:Adaptor Proteins, Signal Transducing; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D010455:Peptides; D051197:Toll-Like Receptor 4