Solid-phase synthesis of CD40L mimetics

The C-3-symmetric molecule 1 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 (143)Lys-Gly-Tyr-Tyr(146) via a 6-aminohexanoic acid residue as a spacer. The present report describes a general solid-phase synthesis approach to 1 and related trimeric architectures. In addition, their CD40 binding properties as well as their effector functions have been evaluated.