Synthesis of 2,2- and 2,5-Disubstituted 1-Oxyl Pyrrolidine Radicals as New Homobifunctional Cross-Linking Spin Labels

Tamás Kálai; József Jekő; Wayne L. Hubbell; Kálmán Hideg

doi:10.1055/s-2003-41053

PAPER

Synthesis of 2,2- and 2,5-Disubstituted 1-Oxyl Pyrrolidine Radicals as New Homobifunctional Cross-Linking Spin Labels

Tamás Kálai^a, József Jekő^b, Wayne L. Hubbell^c, Kálmán Hideg*^a
^a Institute of Organic and Medicinal Chemistry, University of Pécs, 7602 Pécs, P. O. Box 99, Hungary
Fax: +36(72)536219; e-Mail: kalman.hideg@aok.pte.hu;
^b ICN Hungary Ltd., 4440 Tiszavasvári, P. O. Box 1, Hungary
^c Jules Stein Eye Institute and Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095-7008, USA

Abstract

Alle Artikel dieser Rubrik

Abstract

The synthesis of 2,2- and 2,5-disubstituted pyrrolidine nitroxide radicals starting from readily available nitrones 1, 11 is described. The stable radicals are acylating (10, 20), alkylating (7, 17) and thiol-specific (8, 18) reagents capable of producing cross-links in proteins over distances in the range of 10-15 Å.

Key words

cross linking reagents - proteins - free radicals - Grignard reactions - nitrones - lithium

Volltext

Referenzen

References

1 Formaggio F. Bonchio M. Crisma M. Peggion C. Mezzato S. Polese A. Barazza A. Antonello S. Maran F. Broxterman QB. Kaptein B. Kamphuis J. Vitale RM. Saviano M. Benedetti E. Toniolo C. Chem.-Eur. J. 2002, 8: 84

2 Hubbell WL. McConnell HM. J. Am. Chem. Soc. 1971, 93: 314

3 He G. Samouilov A. Kuppusamy A. Zweier JL. J. Magn. Reson. 2001, 148: 155

4 Mitchell JB. Xavier S. DeLuca AM. Showers AL. Cook JA. Krishna MC. Hahn SM. Russo A. Free Radical Biol. Med. 2003, 34: 93

5 Bilski P. Hideg K. Kálai T. Bilska MA. Chignell CF. Free Radical Biol. Med. 2003, 34: 489

6 Hubbell WL. Mchaourab HS. Altenbach C. Lietzow MA. Structure 1996, 4: 779

7 Hubbell WL. Gross A. Langen R. Lietzow MA. Curr. Opin. Struct. Biol. 1998, 8: 649

8 Hubbell WL. Cafiso DS. Altenbach C. Nat. Struct. Biol. 2000, 7: 735

9 Columbus L. Kálai T. Jekő J. Hideg K. Hubbell WL. Biochemistry 2001, 40: 3828

10 Columbus L. Hubbell WL. Trends Biochem. Sci. 2002, 27: 288

11 Kálai T. Rozsnyai B. Jerkovich Gy. Hideg K. Synthesis 1994, 1079

12 Lösel RM. Philipp R. Kálai T. Hideg K. Trommer WE. Bioconjugate Chem. 1999, 10: 578

13 Kálai T. Balog M. Jekő J. Hideg K. Synthesis 1999, 973

14 Kálai T. Balog M. Jekő J. Hubbell WL. Hideg K. Synthesis 2002, 2365

15 Keana JFW. In Spin Labeling II, Theory and Applications Berliner LJ. Academic Press; New York: 1979. p.115

16 Sár PC. Jekő J. Fajer P. Hideg K. Synthesis 1999, 1039

17 Rockenbauer A. Korecz L. Hideg K. J. Chem. Soc., Perkin Trans. 2 1993, 2149

18 Iwahashi H. Parker CE. Mason RP. Tomer KB. Anal. Chem. 1992, 64: 2244

19 Creary X. Aldridge T. J. Org. Chem. 1991, 56: 4280

20 Kocienski P. Protecting Groups 2nd ed.: Thieme; Stuttgart: 2000.

21 Hideg K. Hankovszky HO. Lex L. Kulcsár Gy. Synthesis 1980, 911

22 Hankovszky HO. Hideg K. Lex L. Synthesis 1980, 914

23 Mchaourab HS. Kálai T. Hideg K. Hubbell WL. Biochemistry 1999, 38: 2947

24 Berliner LJ. Grünwald J. Hankovszky HO. Hideg K. Anal. Biochem. 1982, 119: 450

25 Hassner A. Stumer C. In Organic Synthesis Based on Name Reactions and Unnamed Reactions Pergamon; Oxford: 1994. p.89

26 Hill M. Bechet J.-J. d’Albis A. FEBS Lett. 1979, 102: 282