C3-symmetric peptide scaffolds are functional mimetics of trimeric CD40L.

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Serval ID
serval:BIB_74F16518128C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
C3-symmetric peptide scaffolds are functional mimetics of trimeric CD40L.
Journal
Nature Chemical Biology
Author(s)
Fournel S., Wieckowski S., Sun W., Trouche N., Dumortier H., Bianco A., Chaloin O., Habib M., Peter J.C., Schneider P., Vray B., Toes R.E., Offringa R., Melief C.J., Hoebeke J., Guichard G.
ISSN
1552-4450 (Print)
ISSN-L
1552-4450
Publication state
Published
Issued date
2005
Volume
1
Number
7
Pages
377-382
Language
english
Abstract
Interaction between CD40, a member of the tumor necrosis factor receptor (TNFR) superfamily, and its ligand CD40L, a 39-kDa glycoprotein, is essential for the development of humoral and cellular immune responses. Selective blockade or activation of this pathway provides the ground for the development of new treatments against immunologically based diseases and malignancies. Like other members of the TNF superfamily, CD40L monomers self-assemble around a threefold symmetry axis to form noncovalent homotrimers that can each bind three receptor molecules. Here, we report on the structure-based design of small synthetic molecules with C3 symmetry that can mimic CD40L homotrimers. These molecules interact with CD40, compete with the binding of CD40L to CD40, and reproduce, to a certain extent, the functional properties of the much larger homotrimeric soluble CD40L. Architectures based on rigid C3-symmetric cores may thus represent a general approach to mimicking homotrimers of the TNF superfamily.
Keywords
Animals, Antigens, CD40/biosynthesis, Antigens, CD40/chemistry, Apoptosis/drug effects, CD40 Ligand/chemistry, CD40 Ligand/drug effects, Cell Line, Cell Line, Tumor, Humans, Mice, Mice, Inbred BALB C, Models, Biological, Molecular Mimicry/drug effects, Molecular Structure, Peptides/chemistry, Peptides/pharmacology, Protein Conformation, Protein Structure, Quaternary, Structure-Activity Relationship, Time Factors
Pubmed
Web of science
Open Access
Yes
Create date
19/01/2008 17:30
Last modification date
20/08/2019 14:32
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