title: A novel approach to the high-specific-activity labeling of small peptides with the technetium-99m fragment [99mTc(N)(PXP)]2+ (PXP = diphosphine ligand).
abstract: A new labeling approach for incorporating bioactive peptides into a technetium-99m coordination complex is described. This method exploits the chemical properties of the novel metal-nitrido fragment [99mTc(N)(PXP)]2+, composed of a terminal Tc[triple bond] N multiple bond bound to an ancillary diphosphine ligand (PXP). It will be shown that this basic, molecular building block easily forms in solution as the dichloride derivative [99mTc(N)(PXP)Cl2], and that this latter complex selectively reacts with monoanionic and dianionic, bidentate ligands (YZ) having soft, pi-donor coordinating atoms to afford asymmetrical nitrido heterocomplexes of the type [99mTc(N)(PXP)(YZ)]0/+ without removal of the basic motif [99mTc(N)(PXP)]2+. The reactions of the amino acid cysteine was studied in detail. It was found that cysteine readily coordinates to the metal fragment [99mTc(N)(PXP)]2+ either through the [NH2, S-] pair of donor atoms or, alternatively, through the [O-, S-] pair, to yield the corresponding asymmetrical complexes in very high specific activity. Thus, these results were conveniently employed to devise a new, efficient procedure for labeling short peptide sequences having a terminal cysteine group available for coordination to the [99mTc(N)(PXP)]2+ fragment. Examples of the application of this novel approach to the labeling of the short peptide ligand H-Arg-Gly-Asp-Cys-OH (H(2)1) and of the peptidomimetic derivative H-Cys-Val-2-Nal-Met-OH (H2) will be discussed.
authors.affiliation: Laboratory of Nuclear Medicine, Department of Clinical & Experimental Medicine, University of Ferrara, Via L. Borsari, 46, 44100 Ferrara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Boschi
authors.forename: C
authors.initials: C
authors.lastname: Bolzati
authors.forename: E
authors.initials: E
authors.lastname: Benini
authors.forename: E
authors.initials: E
authors.lastname: Malagò
authors.forename: L
authors.initials: L
authors.lastname: Uccelli
authors.forename: A
authors.initials: A
authors.lastname: Duatti
authors.forename: A
authors.initials: A
authors.lastname: Piffanelli
authors.forename: F
authors.initials: F
authors.lastname: Refosco
authors.forename: F
authors.initials: F
authors.lastname: Tisato
mesh_terms: D000588:Amines / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000737:chemistry; D015195:Drug Design; D004355:Drug Stability; D008024:Ligands; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry*; D010720:Phosphines / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D013667:Technetium / Q000737:chemistry*
chemical_list: D000588:Amines; D008024:Ligands; D009842:Oligopeptides; D010720:Phosphines; D019275:Radiopharmaceuticals; D013667:Technetium; D003545:Cysteine