title: Application of metal-free triazole formation in the synthesis of cyclic RGD-DTPA conjugates.
abstract: The tandem 1,3-dipolar cycloaddition-retro-Diels-Alder (tandem crDA) reaction is presented as a versatile method for metal-free chemoselective conjugation of a DTPA radiolabel to N-delta-azido-cyclo(-Arg-Gly-Asp-d-Phe-Orn-) via oxanorbornadiene derivatives. To this end, the behavior of several trifluoromethyl-substituted oxanorbornadiene derivatives in the 1,3-dipolar cycloaddition was studied and optimized to give a clean and efficient method for bio-orthogonal ligation in an aqueous environment. After radioisotope treatment, the resulting 111In-labeled c(RGD)-CF3-triazole-DTPA conjugate was subjected to preliminary biological evaluation and showed high affinity for alpha(v)beta(3) (IC(50)=192 nM) and favorable pharmacokinetics.
authors.affiliation: Institute for Molecules and Materials, Radboud University Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, NL.
authors.forename: Sander S
authors.initials: SS
authors.lastname: van Berkel
authors.forename: A ' Ton ' J
authors.initials: A'
authors.lastname: Dirks
authors.forename: Silvie A
authors.initials: SA
authors.lastname: Meeuwissen
authors.forename: Dennis L L
authors.initials: DL
authors.lastname: Pingen
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
authors.forename: Peter
authors.initials: P
authors.lastname: Laverman
authors.forename: Floris L
authors.initials: FL
authors.lastname: van Delft
authors.forename: Jeroen J L M
authors.initials: JJ
authors.lastname: Cornelissen
authors.forename: Floris P J T
authors.initials: FP
authors.lastname: Rutjes
mesh_terms: D000595:Amino Acid Sequence; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008670:Metals / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D004369:Pentetic Acid / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D013194:Staining and Labeling; D014230:Triazoles / Q000737:chemistry*
chemical_list: D039302:Integrin alphaVbeta3; D008670:Metals; D009842:Oligopeptides; D010456:Peptides, Cyclic; D014230:Triazoles; C047981:arginyl-glycyl-aspartic acid; D004369:Pentetic Acid