title: Synthesis and structural properties of patellamide A derivatives and their copper(II) compounds.
abstract: The synthesis, characterization and copper(II) coordination chemistry of three new cyclic peptide ligands, PatJ(1) (cyclo-(Ile-Thr-(Gly)Thz-Ile-Thr-(Gly)Thz)), PatJ(2) (cyclo-(Ile-Thr-(Gly)Thz-(D)-Ile-Thr-(Gly)Thz)), and PatL (cyclo-(Ile-Ser-(Gly)Thz-Ile-Ser-(Gly)Thz)) are reported. All of these cyclic peptides and PatN (cyclo-(Ile-Ser-(Gly)Thz-Ile-Thr-(Gly)Thz)) are derivatives of patellamide A and have a [24]azacrown-8 macrocyclic structure. All four synthetic cyclic peptides have two thiazole rings but, in contrast to patellamide A, no oxazoline rings. The molecular structure of PatJ(1), determined by X-ray crystallography, has a saddle conformation with two close-to-coparallel thiazole rings, very similar to the geometry of patellamide D. The two coordination sites of PatJ(1) with thiazole-N and amide-N donors are each well preorganized for transition metal ion binding. The coordination of copper(II) was monitored by UV/Vis spectroscopy, and this reveals various (meta)stable mono- and dinuclear copper(II) complexes whose stoichiometry was confirmed by mass spectra. Two types of dinuclear copper(II) complexes, [Cu(2)(H(4)L)(OH(2))(n)](2+) (n=6, 8) and [Cu(2)(H(2)L)(OH(2))(n)] (n=4, 6; L=PatN, PatL, PatJ(1), PatJ(2)) have been identified and analyzed structurally by EPR spectroscopy and a combination of spectra simulations and molecular mechanics calculations (MM-EPR). The four structures are similar to each other and have a saddle conformation, that is, derived from the crystal structure of PatJ(1) by a twist of the two thiozole rings. The small but significant structural differences are characterized by the EPR simulations.
authors.affiliation: Department of Chemistry The University of Queensland Brisbane, Queensland 4072, Australia.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Bernhardt
authors.forename: Peter
authors.initials: P
authors.lastname: Comba
authors.forename: David P
authors.initials: DP
authors.lastname: Fairlie
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Gahan
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Hanson
authors.forename: Lutz
authors.initials: L
authors.lastname: Lötzbeyer
mesh_terms: D000577:Amides / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D008024:Ligands; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D013237:Stereoisomerism
chemical_list: D000577:Amides; D008024:Ligands; D010456:Peptides, Cyclic; D003300:Copper; C085274:patellamide A