Solid-phase synthesis of CD40L mimetics.
The C3-symmetric molecule has been previously shown to mimic CD40 ligand (CD40L) homotrimers and to display effector functions. This molecule consists of a cyclic hexapeptide core containing the repetition of the D-Ala-L-Lys motif. The side chains of the lysine residues have been modified by appending the CD40L-derived sequence 143Lys-Gly-Tyr-Tyr146 via a 6-aminohexanoic acid residue as a spacer. The present report describes a general solid-phase synthesis approach to and related trimeric architectures. In addition, their CD40 binding properties as well as their effector functions have been evaluated.
Bianco
Alberto
A
Institut de Biologie Moléculaire et Cellulaire, UPR 9021 CNRS, Immunologie et Chimie Thérapeutiques, 15 Rue René Descartes, 67084 Strasbourg, France. A.Bianco@ibmc.u-strasbg.fr
Fournel
Sylvie
S
Wieckowski
Sébastien
S
Hoebeke
Johan
J
Guichard
Gilles
G
D017209:Apoptosis / Q000187:drug effects; D023201:CD40 Ligand / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D018716:Molecular Mimicry; D015394:Molecular Structure; D011485:Protein Binding
D023201:CD40 Ligand