title: A one-pot three-component radiochemical reaction for rapid assembly of 125I-labeled molecular probes.
abstract: Nuclear imaging in conjunction with radioactive tracers enables noninvasive measurements of biochemical events in vivo. However, access to tracers remains limited due to the lack of methods for rapid assembly of radiolabeled molecules with the prerequisite biological activity. Herein, we report a one-pot, three-component, copper(II)-mediated reaction of azides, alkynes, and [(125)I]iodide to yield 5-[(125)I]iodo-1,2,3-triazoles. Using a selection of azides and alkynes in a combinatorial approach, we have synthesized a library of structurally diverse (125)I-labeled triazoles functionalized with bioconjugation groups, fluorescent dyes, and biomolecules. Our preliminary biological evaluation suggests that 5-[(125)I]iodo-1,2,3-triazoles are resistant to deiodination in vivo, both as small molecular probes and as antibody conjugates. The ability to incorporate radioactive iodide into triazoles directly from the parent azides and alkynes makes the method broadly applicable and offers the potential to rapidly assemble molecular probes from an array of structurally diverse, and readily available, building blocks.
authors.affiliation: Institute of Nuclear Medicine and Department of Chemistry, University College London, 235 Euston Road (T-5), London NW1 2BU, UK.
authors.forename: Ran
authors.initials: R
authors.lastname: Yan
authors.forename: Kerstin
authors.initials: K
authors.lastname: Sander
authors.forename: Eva
authors.initials: E
authors.lastname: Galante
authors.forename: Vineeth
authors.initials: V
authors.lastname: Rajkumar
authors.forename: Adam
authors.initials: A
authors.lastname: Badar
authors.forename: Mathew
authors.initials: M
authors.lastname: Robson
authors.forename: Ethaar
authors.initials: E
authors.lastname: El-Emir
authors.forename: Mark F
authors.initials: MF
authors.lastname: Lythgoe
authors.forename: R Barbara
authors.initials: RB
authors.lastname: Pedley
authors.forename: Erik
authors.initials: E
authors.lastname: Årstad
mesh_terms: D007457:Iodine Radioisotopes / Q000737:chemistry*; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D011854:Radiochemistry; D013997:Time Factors; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D007457:Iodine Radioisotopes; D015335:Molecular Probes; D014230:Triazoles