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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, 2010Structure of a New Stable Cu(III)/Cyclopeptide Complex byCu K-Edge XAS StudyAlessandro Pratesi 1,2* , Gabriele Giuli 3 , Maria Rita Cicconi 3 ,Tsu-Chien Weng 4 , Giovanni Pratesi 5 , and Mauro Ginanneschi 1,21 Laboratory of Peptide & Protein Chemistry & Biology, Polo Scientifico e Tecnologico,University of Florence, Italy ; 2 Department of Chemistry “Ugo Schiff”, University ofFlorence, 50019, Sesto Fiorentino, Italy; 3 Dipartimento di Scienze della Terra, Universityof Camerino, 62032, Camerino, Italy; 4 European Synchrotron Radiation Facility - ESRF,F-38043, Grenoble, France; 5 Dipartimento di Scienze della Terra, University of Florence,50121, Florence, Italy; * alessandro.pratesi@unifi.itIntroductionCyclic peptides are important tools in medicinal chemistry, as their constrained geometryallows conformational investigations for structure-activity relationship studies in thecharacterization of the active site of proteins. Cyclopeptides are useful versatile scaffolds,as they can be used for conformational investigations in the search ofepitope/pharmacophore models, or metals coordinating ligands. Some cyclic tetrapeptides,containing the sequence Xaa-His-Yaa-His mimicking metalloprotein binding sites, havebeen synthesized by using a rapid and flexible method based on pseudodiluition SPPS.Cyclic tetrapeptides cyclo(Lys-His-βAla-His) (LK13), cyclo(Lys-DHis-βAla-His) (DK13)and cyclo(Gly-βAla-Gly-Lys) (GK13) have been prepared using SPPS. When thecopper(II) coordination compounds of DK13 in aqueous solution were investigated, it wasnoticed that, differently from the preceding ligands, the equilibrium mixture at alkaline pHgave an absorption band in the near UV range and showed a red-orange color. Completespectroscopic analysis (UV, NMR, MS, EPR) and electrochemical experimentsdemonstrated that, at alkaline pH,stable coordinated copper(III) specieswere formed, probably by dioxygenaction on the added Cu(II) ions [1]. Inorder to confirm the presence of Cu 3+species and to clarify the role ofpeptide structure in the mechanism ofthe copper oxidation, Cu K-edgeXANES and EXAFS spectra havebeen collected for three differentcyclo-peptides.Results and DiscussionX-Ray Absorption Spectroscopy(XAS) data have been collected at theID26 beamline of the ESRF storagering (Grenoble, F). Cu K-edgeXANES and EXAFS step scanspectra were acquired in fluorescencemode, monitoring the emitted fluorescencesignal with a high-puritymulti-element Ge detector. Radiationwas monochromatised by means of adouble-crystal Si(311) monochromatorto achieve high-energy resolutionat the Cu K-edge. In order to reduceradiation induced damage of thepeptide samples, spectra have beencollected at 10 K in a He cryostat,and the intensity of the incidentradiation at the sample has beenadjusted by means of Al filters.Fig. 1. Theoretical XANES curves.610