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 ([ 18 F]F-SA) as a novel aromatic sulfonamide-based click chemistry building block. [ 18 F]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 [ 18 F]F-SA (logP = 1.7) allows handling of the radiotracer in aqueous solutions. The versatility of [ 18 F]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 [ 18 F]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) 

Notes

Acknowledgments

The authors are grateful to Mareike Barth, Inge Közle, Stephan Preusche and Tilow Krauss for their excellent technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

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

Personalised recommendations