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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, 2010Nicotianamine and Thermonicotianamine: Supported Synthesisand Chelation AbilityManuel Larrouy, Jean Martinez, and Florine CavelierInstitut des Biomolécules Max Mousseron, UMR 5247 CNRS-UM1-UM2, Place E.Bataillon, Case Courrier 1703, 34095, Montpellier, FranceIntroductionThe nicotianamine (NA), which was first isolated from the leaves of Nicotiana Tabacum L[1] is known as a key biosynthetic precursor of phytosiderophores. Various studies haveproved that NA plays a significant role in the plants physiology as iron, nickel or zinctransporter [2].Due to the importance of NA, we developed a new method to provide easily andquickly synthetic NA [3-9] and analogues for structure-activity relationship studies on thecomplementation of Nicotianamine Synthase (NAS) deficient tomato mutant“Chloronerva”. Using this method, we also synthesized a new natural analogue of NA, thethermonicotianamine (tNA) [10], that was found in the active site of an archeal NAS likeenzyme [11-12]. Chelating ability of this compound was compared to that of NA by MSanalysis of metal-ligand complexes [13].Results and DiscussionThis novel approach involved a first moiety anchored on Wang resin and bearing a freeamine and on the other part, an aldehyde with suitable protecting groups on all otherfunctions (Scheme 1). This later building block will be used twice to construct NA from theleft to the right part of the molecule (Scheme 2). This new method provided NA, the newnatural analogue tNA and non-natural analogues in high yields and purity.Scheme 1. Synthesis of the aldehyde moiety.Scheme 2. Supported synthesis of Nicotianamine.Chelating ability of tNA was investigated and compared to that of NA by MS analysis. Itappeared that NA and tNA are able to chelate quantitatively Cu(II), Ni(II) (Figures 1 and 2)and Co(II) at pH = 7.5. Competition studies of metal chelation with NA and tNA showedthat Cu(II) complexes are formed first, whereas Ni(II) complexes are thermodynamicallymore stable. Moreover tNA seemed to chelate Cu(II) preferentially.66