Amino Acids

, Volume 44, Issue 4, pp 1167–1180 | Cite as

4-[18F]Fluoro-N-methyl-N-(propyl-2-yn-1-yl)benzenesulfonamide ([18F]F-SA): a versatile building block for labeling of peptides, proteins and oligonucleotides with fluorine-18 via Cu(I)-mediated click chemistry

Original Article

Abstract

Cu(I)-mediated [3+2]cycloaddition between azides and alkynes has evolved into a valuable bioconjugation tool in radiopharmaceutical chemistry. We have developed a simple, convenient and reliable radiosynthesis of 4-[18F]fluoro-N-methyl-N-(propyl-2-yn-1-yl)benzenesulfonamide ([18F]F-SA) as a novel aromatic sulfonamide-based click chemistry building block. [18F]F-SA could be prepared in a remotely controlled synthesis unit in 32 ± 5 % decay-corrected radiochemical yield in a total synthesis time of 80 min. The determined lipophilicity of [18F]F-SA (logP = 1.7) allows handling of the radiotracer in aqueous solutions. The versatility of [18F]F-SA as click chemistry building block was demonstrated by the labeling of a model peptide (phosphopeptide), protein (HSA), and oligonucleotide (L-RNA). The obtained radiochemical yields were 77 % (phosphopeptide), 55–60 % (HSA), and 25 % (L-RNA), respectively. Despite the recent emergence of a multitude of highly innovative novel bioconjugation methods for 18F labeling of biopolymers, Cu(I)-mediated click chemistry with [18F]F-SA represents a reliable, robust and efficient radiolabeling technique for peptides, proteins, and oligonucleotides with the short-lived positron emitter 18F.

Keywords

Cu(I)-mediated click chemistry Fluorine-18 Peptides Proteins Oligonucleotides Positron emission tomography (PET) 

References

  1. Berndt M, Pietzsch J, Wuest F (2007) Labeling of low-density lipoproteins using the 18F-labeled thiol-reactive reagent N-[6-(4-[18F]fluorobenzylidene)aminooxyhexyl]maleimide. Nucl Med Biol 34:5–15PubMedCrossRefGoogle Scholar
  2. Burrows CJ, Muller JG (1998) Oxidative nucleobase modifications leading to strand scission. Chem Rev 98:1109–1152PubMedCrossRefGoogle Scholar
  3. Chan TR, Hilgraf R, Sharpless KB, Fokin VV (2004) Polytriazoles as copper(I)-stabilizing ligands in catalysis. Org Lett 6:2853–2855PubMedCrossRefGoogle Scholar
  4. Czernin J, Phelps ME (2002) Positron emission tomography scanning: current and future applications. Annu Rev Med 53:89–112PubMedCrossRefGoogle Scholar
  5. de Bruin B, Kuhnast B, Hinnen F, Yaouancq L, Amessou M, Johannes L, Samson A, Boisgard R, Tavitian B, Dollé F (2005) 1-[3-(2-[18F]fluoropyridin-3-yloxy)propyl]pyrrole-2,5-dione: design, synthesis, and radiosynthesis of a new [18F]fluoropyridine-based maleimide reagent for the labeling of peptides and proteins. Bioconjug Chem 16:406–420PubMedCrossRefGoogle Scholar
  6. de Graaf AJ, Kooijman M, Hennink WE, Mastrobattista E (2009) Nonnatural amino acids for site-specific protein conjugation. Bioconjug Chem 20:1281–1295PubMedCrossRefGoogle Scholar
  7. Debets MF, van Berkel SS, Dommerholt J, Dirks AT, Rutjes FP, van Delft FL (2011) Bioconjugation with strained alkenes and alkynes. Acc Chem Res 44:805–815PubMedCrossRefGoogle Scholar
  8. Devaraj NK, Hilderbrand S, Upadhyay R, Mazitschek R, Weissleder R (2010) Bioorthogonal turn-on probes for imaging small molecules inside living cells. Angew Chem Int Ed Engl 49:2869–2872PubMedCrossRefGoogle Scholar
  9. Donnelly PS, Zanatta SD, Zammit SC, White JM, Williams SJ (2008) ‘Click’ cycloaddition catalysts: copper(I) and copper(II) tris(triazolylmethyl)amine complexes. Chem Commun (Camb) 7:2459–2461CrossRefGoogle Scholar
  10. Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–822PubMedCrossRefGoogle Scholar
  11. Enas JD, Clark RD, VanBrocklin HF (1997) Synthesis of [18-F]RS-15385-FPh: a Potent And Selective Alpha-2 Adrenergic Receptor Ligand. J Label Compd Radiopharm 40:628–630Google Scholar
  12. Flagothier J, Kaisin G, Mercier F, Thonon D, Teller N, Wouters J, Luxen A (2012) Synthesis of two new alkyne-bearing linkers used for the preparation of siRNA for labeling by click chemistry with fluorine-18. Appl Radiat Isot 70:1549–1557PubMedCrossRefGoogle Scholar
  13. Garg PK, Garg S, Zalutsky MR (1991) Fluorine-18 labeling of monoclonal antibodies and fragments with preservation of immunoreactivity. Bioconjug Chem 2:44–49PubMedCrossRefGoogle Scholar
  14. Glaser M, Arstad E (2007) “Click labeling” with 2-[18F]fluoroethylazide for positron emission tomography. Bioconjug Chem 18:989–993PubMedCrossRefGoogle Scholar
  15. Guhlke S, Wester HJ, Bruns C, Stöcklin G (1994) (2-[18F]fluoropropionyl-(D)phe1)-octreotide, a potential radiopharmaceutical for quantitative somatostatin receptor imaging with PET: synthesis, radiolabeling, in vitro validation and biodistribution in mice. Nucl Med Biol 21:819–825PubMedCrossRefGoogle Scholar
  16. Hocke C, Prante O, Löber S, Hübner H, Gmeiner P, Kuwert T (2005) Synthesis and evaluation of 18F-labeled dopamine D3 receptor ligands as potential PET imaging agents. Bioorg Med Chem Lett 15:4819–4823PubMedCrossRefGoogle Scholar
  17. Inkster JA, Guerin B, Ruth TJ, Adam MJ (2008) Radiosynthesis and bioconjugation of [18F]FPy5yne, a prosthetic group for the 18F labeling of bioactive peptides. J Label Compd Radiopharm 51:444–452CrossRefGoogle Scholar
  18. Inkster JA, Adam MJ, Storr T, Ruth TJ (2009) Labeling of an antisense oligonucleotide with [(18)F]FPy5yne. Nucleosides Nucleotides Nucleic Acids 28:1131–1143PubMedCrossRefGoogle Scholar
  19. Kilbourn MR, Dence CS, Welch MJ, Mathias CJ (1987) Fluorine-18 labeling of proteins. J Nucl Med 28:462–470PubMedGoogle Scholar
  20. Köhn M, Breinbauer R (2004) The Staudinger ligation-a gift to chemical biology. Angew Chem Int Ed Engl 43:3106–3116PubMedCrossRefGoogle Scholar
  21. Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed Engl 40:2004–2021PubMedCrossRefGoogle Scholar
  22. Kolthoff IM (1925) A new set of buffer mixtures that can be prepared without the use of standardized acid or base. J Bio Chem 63:135–141Google Scholar
  23. Kostikov AP, Chin J, Orchowski K, Niedermoser S, Kovacevic MM, Aliaga A, Jurkschat K, Wängler B, Wängler C, Wester HJ, Schirrmacher R (2012) Oxalic acid supported Si-18F-radiofluorination: one-step radiosynthesis of N-succinimidyl 3-(di-tert-butyl[18F]fluorosilyl)benzoate ([18F]SiFB) for protein labeling. Bioconjug Chem 23:106–114PubMedCrossRefGoogle Scholar
  24. Kuhnast B, Dolle F (2010) The challenge of labelling macromolecules with fluorine-18: three decades of research. Curr Radiopharm 3:174–201CrossRefGoogle Scholar
  25. Kuhnast B, Hinnen F, Tavitian B, Dolle F (2008) [18F]FPyKYNE, a fluoropyridine-based alkyne reagent designed for the fluorine-18 labelling of macromolecules using click chemistry. J Label Compd Radiopharm 51:336–342CrossRefGoogle Scholar
  26. Liao J (2007) Protein and cellular engineering with unnatural amino acids. Biotechnol Prog 23:28–31PubMedCrossRefGoogle Scholar
  27. Liu S, Shen B, Chin FT, Cheng Z (2011) Recent progress in radiofluorination of peptides for PET molecular imaging. Curr Org Chem 8:584–592Google Scholar
  28. Liu DS, Tangpeerachaikul A, Selvaraj R, Taylor MT, Fox JM, Ting AY (2012) Diels-Alder cycloaddition for fluorophore targeting to specific proteins inside living cells. J Am Chem Soc 134:792–879PubMedCrossRefGoogle Scholar
  29. Mamat C, Ramenda T, Wuest F (2009) Application of click chemistry for the synthesis of radiotracers for molecular imaging. Mini Rev Org Chem 6:21–34CrossRefGoogle Scholar
  30. Marik J, Sutcliffe JL (2006) Click for PET: rapid preparation of [18F]fluoropeptides using CuI catalyzed 1,3-dipolar cycloaddition. Tetrahedron Lett 47:6681–6684CrossRefGoogle Scholar
  31. McBride WJ, D’Souza CA, Karacay H, Sharkey RM, Goldenberg DM (2012) New lyophilized kit for rapid radiofluorination of peptides. Bioconjug Chem 23:538–547PubMedCrossRefGoogle Scholar
  32. Okarvi SM (2001) Recent progress in fluorine-18 labelled peptide radiopharmaceuticals. Eur J Nucl Med 28:929–938PubMedCrossRefGoogle Scholar
  33. Olberg DE, Hjelstuen OK (2010) Labeling strategies of peptides with 18F for positron emission tomography. Curr Top Med Chem 10:1669–1679PubMedCrossRefGoogle Scholar
  34. Paans AM, van Waarde A, Elsinga PH, Willemsen AT, Vaalburg W (2002) Positron emission tomography: the conceptual idea using a multidisciplinary approach. Methods 27:195–207PubMedCrossRefGoogle Scholar
  35. Phelps ME (2000) PET: the merging of biology and imaging into molecular imaging. J Nucl Med 41:661–681PubMedGoogle Scholar
  36. Poethko T, Schottelius M, Thumshirn G, Hersel U, Herz M, Henriksen G, Kessler H, Schwaiger M, Wester HJ (2004) Two-step methodology for high-yield routine radiohalogenation of peptides: (18)F-labeled RGD and octreotide analogs. J Nucl Med 45:892–902PubMedGoogle Scholar
  37. Ramenda T, Bergmann R, Wuest F (2007) Synthesis of 18F-labeled neurotensin(8–13) via copper-mediated 1,3-dipolar [3+2]cycloaddition reaction. Lett Drug Des Discov 4:279–285CrossRefGoogle Scholar
  38. Richter S, Bergmann R, Pietzsch J, Ramenda T, Steinbach J, Wuest F (2009) Fluorine-18 labeling of phosphopeptides: a potential approach for the evaluation of phosphopeptide metabolism in vivo. Biopolymers 92:479–488PubMedCrossRefGoogle Scholar
  39. Richter S, Ramenda T, Bergmann R, Kniess T, Steinbach J, Pietzsch J, Wuest F (2010) Synthesis of neurotensin(8–13)-phosphopeptide heterodimers via click chemistry. Bioorg Med Chem Lett 20:3306–3309PubMedCrossRefGoogle Scholar
  40. Roivainen A, Tolvanen T, Salomäki S, Lendvai G, Velikyan I, Numminen P, Välilä M, Sipilä H, Bergström M, Härkönen P, Lönnberg H, Långström B (2004) 68 Ga-labeled oligonucleotides for in vivo imaging with PET. J Nucl Med 45:347–355PubMedGoogle Scholar
  41. Rostovtsev VV, Green LG, Fokin VV, Sharpless KB (2002) A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew Chem Int Ed Engl 41:2596–2599PubMedCrossRefGoogle Scholar
  42. Schirrmacher R, Bradtmöller G, Schirrmacher E, Thews O, Tillmanns J, Siessmeier T, Buchholz HG, Bartenstein P, Wängler B, Niemeyer CM, Jurkschat K (2006) 18F-labeling of peptides by means of an organosilicon-based fluoride acceptor. Angew Chem Int Ed Engl 45:6047–6050PubMedCrossRefGoogle Scholar
  43. Seo TS, Li Z, Ruparel H, Ju J (2003) Click chemistry to construct fluorescent oligonucleotides for DNA sequencing. J Org Chem 68:609–612PubMedCrossRefGoogle Scholar
  44. Shiue CY, Shiue GG, Bernard F, Greenberg JH (1999) Comparative studies of F-18 labeled benzamides and arylsulfonamides as sigma receptor ligands. J Label Compd Radiopharm 42:S108–S110Google Scholar
  45. Still WC, Kahn M, Mitra A (1978) Rapid chromatographic technique for preparative separation with moderate resolution. J Org Chem 43:2923–2925CrossRefGoogle Scholar
  46. Supuran CT, Alies MA, Scozzafava A (1998) Carbonic anhydrase inhibitors—Part 29: interaction of isozymes I, II and IV with benzolamide-like derivatives. Eur J Med Chem 33:739–751CrossRefGoogle Scholar
  47. Tang S, Verdurand M, Joseph B, Lemoine L, Daoust A, Billard T, Fournet G, Le Bars D, Zimmer L (2007) Synthesis and biological evaluation in rat and cat of [18F]12ST05 as a potential 5-HT6 PET radioligand. Nucl Med Biol 34:995–1002PubMedCrossRefGoogle Scholar
  48. Tavitian B (2003) In vivo imaging with oligonucleotides for diagnosis and drug development. Gut 52(Suppl 4):iv40–iv47Google Scholar
  49. Thonon D, Kech C, Paris J, Lemaire C, Luxen A (2009) New strategy for the preparation of clickable peptides and labeling with 1-(azidomethyl)-4-[(18)F]-fluorobenzene for PET. Bioconjug Chem 20:817–823PubMedCrossRefGoogle Scholar
  50. Toyokuni T, Walsh JC, Dominguez A, Phelps ME, Barrio JR, Gambhir SS, Satyamurthy N (2003) Synthesis of a new heterobifunctional linker, N-[4-(aminooxy)butyl]maleimide, for facile access to a thiol-reactive 18F-labeling agent. Bioconjug Chem 14:1253–1259PubMedCrossRefGoogle Scholar
  51. Vaidyanathan G, Zalutsky MR (1992) Labeling proteins with fluorine-18 using N-succinimidyl 4-[18F]fluorobenzoate. Int J Rad Appl Instrum B 19:275–281PubMedCrossRefGoogle Scholar
  52. van Berkel SS, van Eldijk MB, van Hest JC (2011) Staudinger ligation as a method for bioconjugation. Angew Chem Int Ed Engl 50:8806–8827PubMedCrossRefGoogle Scholar
  53. van Hest JC, van Delft FL (2011) Protein modification by strain-promoted alkyne-azide cycloaddition. ChemBioChem 12:1309–1312PubMedCrossRefGoogle Scholar
  54. Voloshchuk N, Montclare JK (2010) Incorporation of unnatural amino acids for synthetic biology. Mol BioSyst 6:65–80PubMedCrossRefGoogle Scholar
  55. Wa C, Cerny R, Hage DS (2006) Obtaining high sequence coverage in matrix-assisted laser desorption time-of-flight mass spectrometry for studies of protein modification: analysis of human serum albumin as a model. Anal Biochem 349:229–241PubMedCrossRefGoogle Scholar
  56. Wängler C, Schirrmacher R, Bartenstein P, Wängler B (2010) Click-chemistry reactions in radiopharmaceutical chemistry: fast & easy introduction of radiolabels into biomolecules for in vivo imaging. Curr Med Chem 17:1092–1116PubMedCrossRefGoogle Scholar
  57. Wester HJ, Hamacher K, Stöcklin G (1996) A comparative study of N.C.A. fluorine-18 labeling of proteins via acylation and photochemical conjugation. Nucl Med Biol 23:365–372PubMedCrossRefGoogle Scholar
  58. Wilson AA, Jin L, Garcia A, DaSilva JN, Houle S (2001) An admonition when measuring the lipophilicity of radiotracers using counting techniques. Appl Radiat Isot 54:203–208PubMedCrossRefGoogle Scholar
  59. Wuest F (2005) Aspects of positron emission tomography radiochemistry as relevant for food chemistry. Amino Acids 29:323–339PubMedCrossRefGoogle Scholar
  60. Wuest F, Köhler L, Berndt M, Pietzsch J (2009) Systematic comparison of two novel, thiol-reactive prosthetic groups for 18F labeling of peptides and proteins with the acylation agent succinimidyl-4-[18F]fluorobenzoate ([18F]SFB). Amino Acids 36:283–295PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  1. 1.Institute of RadiopharmacyHelmholtz-Zentrum Dresden-RossendorfDresdenGermany
  2. 2.CUP Laboratorien Dr. Freitag GmbHRadebergGermany
  3. 3.Department of OncologyUniversity of AlbertaEdmontonCanada

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