title: Backbone metal-cyclization: a novel approach for simultaneous peptide cyclization and radiolabeling. Application to the combinatorial synthesis of rhenium-cyclic somatostatin analogs.
abstract: A novel approach for the combinatorial synthesis of backbone-derived metal-cyclic peptide libraries is presented. In this approach the metalo-cyclic peptides are prepared from their linear precursors through complexation of a metal atom via two hemi-chelating arms located on the peptide backbone. Thus, cyclization and metal labeling of the peptides are achieved simultaneously. A library, composed of 48 rhenium-cyclic somatostatin analogs, was prepared. All rhenium somatostatin complexes exhibited high to moderate in vitro binding affinities toward cloned human somatostatin receptor subtype 2 (hsstr2). Five rhenium-cyclic peptides were found to be most potent with IC50 values between 1 and 3 nM making them promising leads for further development of tumor diagnostic and therapeutic radiolabeled agents. A 99mTc somatostatin cyclic analog was successfully prepared by the same method.
authors.affiliation: Department of Organic Chemistry, Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Fridkin
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bonasera
authors.forename: Pninit
authors.initials: P
authors.lastname: Litman
authors.forename: Chaim
authors.initials: C
authors.lastname: Gilon
mesh_terms: D001665:Binding Sites; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D015195:Drug Design; D005240:Feasibility Studies; D006207:Half-Life; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D008670:Metals / Q000737:chemistry; D019151:Peptide Library; D011485:Protein Binding; D011868:Radioisotopes / Q000737:chemistry*; D017481:Receptors, Somatostatin / Q000737:chemistry*; D012211:Rhenium / Q000737:chemistry*; D013004:Somatostatin / Q000031:analogs & derivatives*
chemical_list: D008670:Metals; D019151:Peptide Library; D011868:Radioisotopes; D017481:Receptors, Somatostatin; D013004:Somatostatin; D012211:Rhenium; C093733:somatostatin receptor 2