title: DOTA-Derivatives of Octreotide Dicarba-Analogs with High Affinity for Somatostatin sst2,5Receptors.
abstract: In vivosomatostatin receptor scintigraphy is a valuable method for the visualization of human endocrine tumors and their metastases. In fact, peptide ligands of somatostatin receptors (sst's) conjugated with chelating agents are in clinical use. We have recently developed octreotide dicarba-analogs, which show interesting binding profiles at sst's. In this context, it was mandatory to explore the possibility that our analogs could maintain their activity also upon conjugation with DOTA. In this paper, we report and discuss the synthesis, binding affinity and conformational preferences of three DOTA-conjugated dicarba-analogs of octreotide. Interestingly, two conjugated analogs exhibited nanomolar affinities on sst2and sst5somatostatin receptor subtypes.
authors.affiliation: Department of Chemistry "Ugo Schiff," University of Florence Firenze, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pratesi
authors.affiliation: Department of Chemistry "Ugo Schiff," University of FlorenceFirenze, Italy; Interdepartmental Laboratory of Peptide & Protein Chemistry & Biology, University of FlorenceFirenze, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Ginanneschi
authors.affiliation: Department of Chemistry "Ugo Schiff," University of FlorenceFirenze, Italy; Interdepartmental Laboratory of Peptide & Protein Chemistry & Biology, University of FlorenceFirenze, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lumini
authors.affiliation: Department of Chemistry "Ugo Schiff," University of FlorenceFirenze, Italy; Interdepartmental Laboratory of Peptide & Protein Chemistry & Biology, University of FlorenceFirenze, Italy.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Papini
authors.affiliation: Department of Pharmacy, University of Naples "Federico II" Naples, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.affiliation: Department of Pharmacy, University of Naples "Federico II" Naples, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Brancaccio
authors.affiliation: Department of Pharmacy, University of Naples "Federico II" Naples, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Carotenuto
keywords: DOTA-conjugation; NMR conformational analysis; dicarba-analogs; radiotracers; somatostatin receptors