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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010NHDesign and Synthesis of Bipyridyl-Containing PeptideDendrimers as Iron Protein ModelsPiero Geotti-Bianchini, Nicolas A. Uhlich, Tamis Darbre, andJean-Louis Reymond*Department of Chemistry and Biochemistry, University of Berne, Freiestrasse 3,3012, Berne, SwitzerlandIntroductionPeptide dendrimers, containing diamino acids as branching units [1], possess suitableproperties as soluble protein models, such as a hindered, solvent-shielded core and multipleperipheral groups [2]. Since peptide dendrimers are composed of amino acids, theirchemico-physical properties, hence their activity, are easily tunable by sequencemodification or introduction of non-natural amino acids [3]. Bipyridyl is a bidentate ligandwith high affinity for late transition metals, forming very stable 3:1 complexes with Fe(II).In such complexes the valence of the metal center is saturated, whereas in iron enzymescoordinative unsaturatation is required for activity [4]. Therefore, in our research onmetalloenzyme models, we have studied the effect of the incorporation of bipyridyl units inpeptide dendrimers, aiming at a control of binding selectivity and stoichiometry.NNOBpyFig. 1. The bipyridyl derivedamino acid Bpy.We have recently reported [5] the synthesis of abipyridyl-based amino acid (Bpy, Figure 1) and itsincorporation in the focal point of a combinatorial library ofpeptide dendrimers (Figure 2, top left, structure 1). Metalbinding experiments showed that 3:1 dendrimer/Fe(II)complexes were formed by negatively charged sequences,but not by strongly positively charged ones.Results and DiscussionWe have then prepared second generation peptide dendrimers carrying Bpy in the twofirst-generation branches (Figure 2, bottom left, structure 2), expecting stronger metalbinding and a more pronounced effect of the dendrimer composition on the metalcomplexation properties.Fig. 2. Left: Structure of the peptide dendrimers carrying one Bpy residue in the focalpoint (1, top) or two Bpy residues in the two first generation branches (2, bottom). Blackdots represent the branching residues (2,3-diamino-propionic acid), AA n (n= 1-6)represent the variable amino acids (specified in Table 1). Right: Spectrophotometrictitration of dendrimer 2a (30 µM) with Fe(II) in HEPES buffer (top); Job plot analysis ofFe(II) binding for the same dendrimer at a total concentration of 30 µM (bottom).624