Peptide-chelating agent conjugate for selective targeting of somatostatin receptor type 1: Synthesis and characterization(514 views) Mansi R, Tesauro D, De Capua A, Fattorusso R, Carac C, Aloj L, Benedetti E, Morelli G
Keywords: Indium Complexes, Nuclear Medicine Techniques, Somatostatin Analogue, Binding Energy, Biosynthesis, Chelation, Coordination Reactions, Imaging Techniques, Radioactivation Analysis, Tumors, Chelating Agents, Lesions, Peptide-Chelating Agent, Polypeptides, 9 Fluorenylmethyl Chloroformate, Glutamic Acid Derivative, Glycine, Indium 111, Iodine 125, Metal Derivative, N Bis[2 [bis(carboxyethyl)amino]ethyl]glutamic Acid Glycine Somatostatin[8 Dextro Tryptophan 9 N Isopropylaminomethylphenylalanine], N Bis[2 [bis(carboxyethyl)amino]ethyl]glutamic Acid Glycine Somatostatin[8 Dextro Tryptophan 9 N Isopropylaminomethylphenylalanine] In 111, Pentetic Acid, Pentetic Acid Derivative, Peptide Derivative, Radioactive Material, Somatostatin Derivative, Somatostatin Receptor 1, Unclassified Drug, Amino Terminal Sequence, Animal Cell, Binding Competition, Bioassay, Concentration Response, Conference Paper, Conjugate, Drug Conformation, Drug Receptor Binding, Drug Selectivity, Drug Synthesis, Drug Targeting, Gene Overexpression, Isotope Labeling, Nonhuman, Nuclear Magnetic Resonance, Receptor Affinity, Reversed Phase High Performance Liquid Chromatography, Scintigraphy, Stereospecificity, Structure Activity Relation, Amino Acid Sequence, Indium Radioisotopes, Radiopharmaceuticals, N Bis [2 [bis (carboxyethyl) Amino] Ethyl] Glutamic Acid Glycine Somatostatin [8 Dextro Tryptophan 9 N Isopropylaminomethylphenylalanine], N Bis [2 [bis (carboxyethyl) Amino] Ethyl] Glutamic Acid Glycine Somatostatin [8 Dextro Tryptophan 9 N Isopropylaminomethylphenylalanine] In 111,
Affiliations: *** IBB - CNR ***
Department of Biological Chemistry, Interuniv. Res. Ctr. B. P. (CIRPeB), University of Naples Federico II, Via Mezzocannone, 6/8, I-80134 Naples, Italy
Department of Environmental Sciences, Second University of Naples, Via Arena, 8, 81100 Caserta, Italy
Inst. of Biostructures/Bioimaging, CNR, Via Mezzocannone, 6/8, 1-80134 Naples, Italy
References: Not available.
Peptide-chelating agent conjugate for selective targeting of somatostatin receptor type 1: Synthesis and characterization
Previously reported results suggest that the analogue of the somatostatin des-AA(1,2,5) [D-Trp(8),Imp(9)]-somatostatin (CH-275) peptide bearing chelating agents able to coordinate radioactive metals could be used for scintigraphic imaging of tumor lesions overexpressing sstr1. An efficient synthetic procedure for the preparation of the somatostatin analogue CH-275 and its conjugate DTPAGlu-Gly-CH-275, bearing the chelating agent DTPAGlu (DTPAGlu = N,N-bis[2-[bis(carboxy-ethyl)amino]ethyl]-L-glutamic acid) on the N-terminus, by solid-phase peptide synthesis and 9-flourenymethyoxycarbonyl (Fmoc) chemistry, is here reported. Rapid and efficient labeling of DTPAGlu-Gly-CH-275 was achieved by addition of In-III(III) to the compound. Typical yields were greater than 97% as determined by reversed phase high performance liquid chromatography (HPLC) at specific activities in the range 4-9 GBq/mumol (100-250 Ci/mmol). A preliminary biological assay of the binding ability of In-III-DTPAGlu-Gly-CH-275 indicates, however, that the labeled compound does not display any specific interaction with somatostatin sstr1 receptors in the tested cell lines. To confirm this unexpected negative result, competition binding experiments were carried out, in which fixed tracer amounts of the I-125-labeled somatostatin-14 were incubated with the receptor-expressing cells in the presence of DTPAGlu-Gly-CH-275 or CH-275 at concentrations ranging from 10(-10) to 10(-3) M. While CH-275 shows a IC50 of 80 nM similar to that already found in displacement experiments on CHO-K1 sstr1-transfected cells, DTPAGlu-Gly-CH-275 displays instead very low or negligible affinity towards this receptor. The NMR solution characterization indicates that the presence of DTPAGlu does not influence the conformational and chemical features of the peptide moiety, thus suggesting that the loss in binding activity should be due to steric hindrance of either the chelating agent DTPAGlu or its indium complex. (C) 2004 Wiley Periodicals, Inc.
Peptide-chelating agent conjugate for selective targeting of somatostatin receptor type 1: Synthesis and characterization
No results.
Peptide-chelating agent conjugate for selective targeting of somatostatin receptor type 1: Synthesis and characterization