title: Synthesis of rhenium-centric reverse turn mimics.
abstract: Molecular scaffolds have been shown to facilitate and stabilise secondary structural turn elements, with a central core-arranging functionality in a defined three-dimensional orientation. In a peptide-based molecular imaging probe, this approach is of particular value as it would essentially "hide" a metal radioisotope within the ligand framework, making the labelling element a critical component of the receptor-bound structure. Starting from a 1,2-diaminoethane loaded 2-chlorotrityl resin, a versatile set of triamine ligand systems were synthesised by using solid-phase Fmoc-based peptide chemistry. The resultant resin-bound peptides then underwent amide reduction by treatment with borane-THF at 65 °C. This provided complete conversion to the corresponding polyamine entities in high purity for the majority of the amino acids utilised. The triamines were then coordinated on solid support by using [NEt(4)](2)[Re(CO)(3)(Br)(3)] followed by resin cleavage and HPLC purification, to give the desired rhenium coordinated species. We have shown that amino acid sequences can be assembled, reduced and coordinated on-resin, resulting in a versatile set of metal-ligand constructs. These studies could be expanded to generate libraries of turn-based peptidomimetics containing Re/Tc(I) organometallic scaffolds, with the intention of developing an improved approach for finding new diagnostic and therapeutic radiopharmaceutical entities.
authors.affiliation: Department of Chemistry, University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 5B7, Canada.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hickey
authors.forename: Leonard G
authors.initials: LG
authors.lastname: Luyt
mesh_terms: D002851:Chromatography, High Pressure Liquid; D008024:Ligands; D008670:Metals / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011868:Radioisotopes / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry*; D012211:Rhenium / Q000737:chemistry*
chemical_list: D008024:Ligands; D008670:Metals; D009942:Organometallic Compounds; D010455:Peptides; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012211:Rhenium