title: Biotin derivatives carrying two chelating DOTA units. Synthesis, in vitro evaluation of biotinidases resistance, avidin binding, and radiolabeling tests.
abstract: The synthesis of four biotin derivatives carrying two DOTA moieties for each ligand (BisDOTA set) is reported, for increasing radiation/dose ratio and improving efficiency in the pretargeted avidin-biotin radioimmunotherapy. The biotin-containing scaffold of two BisDOTA was similar to the mono-DOTA derivative previously described. Then the scaffold was elongated by trifunctionalized spacers of different length and conjugated with one of the COOH groups of two DOTA. Two others were prepared starting from a on-resin lysine residue. The lysine alpha-NH2 was bonded to biotin, and then spacers were appended to the epsilon-NH2 and conjugated with two DOTA molecules. One compound contained a p-aminobenzoic acid spacer, which ensured higher head-to-tail distance and increased rigidity of the chain. These last two compounds had a very high ability to bond avidin and were labeled with 90Y at high specific activity. All the compounds were resistant to the action of serum biotinidases.
authors.affiliation: Laboratory of Chemistry and Biology of Peptides and Proteins, Department of Organic Chemistry "Ugo Schiff", Via della Lastruccia 13, 50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pratesi
authors.forename: Francesca
authors.initials: F
authors.lastname: Bucelli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Mori
authors.forename: Marco
authors.initials: M
authors.lastname: Chinol
authors.forename: Antonio
authors.initials: A
authors.lastname: Verdoliva
authors.forename: Giovanni
authors.initials: G
authors.lastname: Paganelli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Rivieccio
authors.forename: Lucia
authors.initials: L
authors.lastname: Gariboldi
authors.forename: Mauro
authors.initials: M
authors.lastname: Ginanneschi
mesh_terms: D000818:Animals; D001360:Avidin / Q000737:chemistry*; D001665:Binding Sites; D001710:Biotin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002614:Chelating Agents / Q000737:chemistry*; D007553:Isotope Labeling; D051379:Mice; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002614:Chelating Agents; C405616:DOTA-biotin; D009942:Organometallic Compounds; D001360:Avidin; D001710:Biotin