title: Radiolabeled antagonistic bombesin peptidomimetics for tumor targeting.
abstract: The replacement of amide bonds in the backbone of peptides by proteolytically stable 1,2,3-triazole isosteres can provide novel peptidomimetics with promising properties for the development of tumor-targeting radiopeptides. On the basis of our previous work with radiolabeled agonistic bombesin (BBN) derivatives of the sequence [Nle(14) ]BBN(7-14), we substituted selected amide bonds of the structurally closely related antagonistic peptide analog JMV594. With the exception of the C-terminal modification, amide-to-triazole substitutions tolerated by [Nle(14) ]BBN(7-14) without loss of biological function led to abolished receptor affinity in the case of JMV594. These findings provide an additional piece of evidence for the currently disputed differences in the modes of action of agonistic and antagonistic gastrin-releasing peptide receptor (GRPR)-targeting radiopeptides.
authors: Department of Radiology and Nuclear Medicine, University of Basel Hospital, Division of Radiopharmaceutical Chemistry, Petersgraben 4, 4031, Basel, Switzerland.
authors: Ibai E
authors: IE
authors: Valverde
authors: Elena
authors: E
authors: Huxol
authors: Thomas L
authors: TL
authors: Mindt
mesh_terms: D000595:Amino Acid Sequence; D001839:Bombesin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D007553:Isotope Labeling; D008187:Lutetium; D008297:Male; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D057786:Peptidomimetics / Q000737:chemistry / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging*; D059748:Proteolysis; D011868:Radioisotopes; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014230:Triazoles / Q000737:chemistry
chemical_list: D006573:Heterocyclic Compounds, 1-Ring; D010446:Peptide Fragments; D057786:Peptidomimetics; D011868:Radioisotopes; D014230:Triazoles; C118536:bombesin (7-14); C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D008187:Lutetium; D001839:Bombesin
keywords: 1,2,3-triazoles; amide bond mimics; antagonists; bombesin; click chemistry; peptidomimetics; radiopeptides