Solid-phase synthesis of hydroxyproline-based cyclic hexapeptides

Cyclic peptides are excellent tools to investigate the functional and spatial requirements for ligands to bind to a given target. In this paper we report the synthesis of a library of cyclic hexapeptides, designed to be Selectin antagonists. Based on molecular modelling calculations, these peptides contain a hydroxyproline building block that serves also as the point of attachment to the solid phase. A modified THP linker has been prepared to bind the hydroxy group of this amino acid to aminomethyl SynPhase™ Lanterns. Amino acids of the d- and l-series are used and their influence onto the cyclisation step is also investigated.