Download PDF
Synlett 2005(13): 1984-1994  
DOI: 10.1055/s-2005-871950
ACCOUNT
© Georg Thieme Verlag Stuttgart · New York

The Metal-Conjugated Peptide Nucleic Acid Challenge

Clara Baldolia, Paolangelo Cereab, Clelia Gianninib, Emanuela Licandrob, Clara Rigamontib, Stefano Maiorana*b
a CNR - Institute of Molecular Science and Technologies, Via C. Golgi 19, 20133 Milano, Italy
b Department of Organic and Industrial Chemistry and Centre of Excellence CISI, University of Milan, Via C. Golgi 19, 20133 Milano, Italy
Fax: +39(02)50314139; e-Mail: stefano.maiorana@unimi.it;
Further Information

Publication History

Received 27 April 2005
Publication Date:
12 July 2005 (online)

    Permissions and Reprints All articles of this category

Abstract

This Account describes the advances in the chemistry of metal-conjugated peptide nucleic acids (PNAs) obtained in our laboratories over the last three years. Our interest in bioorganometallic chemistry began several years ago and led to new PNA research, including the design, synthesis and study of the properties of metal-conjugated PNAs with the aim of providing new molecules with suitable spectroscopic or electrochemical markers that may be ­useful in biomedical diagnostics. We describe three classes of ­metal-conjugated PNA monomers: Fischer-type carbene complexes (FTC), arene chromium tricarbonyl complexes (ACT) and ferro­cene (Fc), all of which are inserted on the α-carbon of the glycine unit in order to provide chiral substrates as well as the chemical and spectroscopic properties of the adducts. In addition, we have obtained a lysine-containing PNA 10-mer conjugated to a FTCC, in which the presence of the organometallic unit seems to stabilise the duplex with a complementary DNA strand. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) studies of mono- and tris-Fc labelled tyrosine PNA monomers have shown constantly reversible signals with high currents; the almost tripled current intensity of the tris-Fc monomer allows a detection limit of 10-8.

  • 1 Introduction

  • 2 Bioorganometallic Chemistry and Research Origins

  • 3 DNA, RNA and PNA

  • 4 Metal-Conjugated PNAs

  • 4.1 Fischer-Type Carbene-Conjugated PNAs (FTC-PNAs)

  • 4.2 Arene Chromium Tricarbonyl-Conjugated PNAs
    (ACT-PNAs)

  • 4.3 Ferrocene-Conjugated PNAs (Fc-PNAs)

  • 5 Conclusions and Outlook

Key words

PNA - bio-organometallic chemistry - ferrocene - arene chromium tricarbonyl - Fischer-type carbene complexes

    References

  • 1a Peptide Nucleic Acids: Protocols and Applications   2nd ed.:  Nielsen PE. Horizon Bioscience; Wymondham, UK: 2004. 
    CrossrefPubMedGoogle Scholar
  • 1b Uhlmann E. Peyman A. Breipohl G. David W. Angew. Chem. Int. Ed.  1998,  37:  2796 
    CrossrefPubMedGoogle Scholar
  • 2 Nielsen PE. Egholm M. Berg RH. Buchrdt O. Science  1991,  254:  1497 
    CrossrefPubMedGoogle Scholar
  • 3a Gillois J. Buisson D. Azerad R. Jaouen G. J. Chem. Soc., Chem. Commun.  1988,  1284 
    CrossrefGoogle Scholar
  • 3b Gillois J. Buisson D. Azerad R. Jaouen G. J. Organomet. Chem.  1989,  367:  85 
    CrossrefGoogle Scholar
  • 4 Top S. Jaouen G. Gillois J. Baldoli C. Maiorana S. J. Chem. Soc., Chem. Commun.  1988,  1284 
    CrossrefGoogle Scholar
  • 5 Top S. Jaouen G. Baldoli C. Del Buttero P. Maiorana S. J. Organomet. Chem.  1991,  413:  125 
    CrossrefGoogle Scholar
  • 6a Baldoli C. Maiorana S. Carrea G. Riva S. Tetrahedron: Asymmetry  1993,  4:  767 
    CrossrefGoogle Scholar
  • 6b Baldoli C. Del Buttero P. Maiorana S. Ottolina G. Riva S. Tetrahedron: Asymmetry  1998,  9:  1497 
    CrossrefGoogle Scholar
  • 7a Bioorganometallics   1st ed.:  Jaouen G. Wiley-VCH; Weinheim: 2005. 
    Google Scholar
  • 7b Foreword to the special JOMC issue on bioorganometallic chemistry: Jaouen G. Fish RH. J. Organomet. Chem.  2003,  668:  1 
    Google Scholar
  • 7c Beck W. Severin K. Chem. Unserer Zeit  2002,  36:  356 
    Google Scholar
  • 7d Metzler-Nolte N. Angew. Chem. Int. Ed.  2001,  40:  1040 
    Google Scholar
  • 7e Beck W. Dialer H. Steglich W. Z. Naturforsch., B  2001,  56:  1084 
    Google Scholar
  • 7f

    Special Issue on Second International Symposium on Bio-organometallic Chemistry: J. Organomet. Chem. 2004, 689.
  • 8 Salmain M. Licandro E. Baldoli C. Maiorana S. Tran-Huy H. Jaouen G. J. Organomet. Chem.  2001,  617:  376 
    CrossrefGoogle Scholar
  • 9 Sforza S. Tedeschi T. Corradini R. Ciavardelli D. Dossena A. Marchelli R. Eur. J. Org. Chem.  2003,  1056 ; and references cited therein
    CrossrefGoogle Scholar
  • 10 Wang J. Nucleic Acids Res.  2000,  28:  3011 ; and references cited therein
    CrossrefGoogle Scholar
  • 11a Egholm M. Buchardt O. Christensen L. Behrens C. Freier SM. Driver DA. Berg RH. Kim SK. Nordén B. Nielsen PE. Nature (London)  1993,  365:  556 
    CrossrefGoogle Scholar
  • 11b Tomac S. Sakar M. Ratilainen T. Wittung P. Niesen PE. Nordén B. Graslund A. J. Am. Chem. Soc.  1996,  118:  5544 
    CrossrefGoogle Scholar
  • 11c Giesen U. Kleider W. Berding C. Geiger A. Ørum H. Nielsen PE. Nucleic Acids Res.  1998,  26:  5004 
    CrossrefGoogle Scholar
  • 12a Kerman K. Ozkan D. Kara P. Erden A. Meric B. Nielsen PE. Ozsoz M. Electroanalysis  2003,  15:  667 
    CrossrefGoogle Scholar
  • 12b Basile A. Giuliani A. Pirri G. Chiari M. Electrophoresis  2002,  23:  926 
    CrossrefGoogle Scholar
  • 12c Corradini R. Feriotto G. Sforza S. Marchelli R. Gambari R. J. Mol. Recognit.  2004,  17:  76 
    CrossrefGoogle Scholar
  • 13a Pooga M. Soomets U. Hallbrink M. Valkna A. Saar K. Rezaei K. Kahl U. Hao J.-X. Xu X.-J. Wiesenfeld-Hallin Z. Hokfelt T. Bartfai T. Langel U. Nature Biotechnol.  1998,  16:  857 
    CrossrefGoogle Scholar
  • 13b Tyler BM. McCormick DJ. Hoshall CV. Douglas CL. Jansen K. Lacy BW. Cusack B. Richelson E. FEBS Lett.  1998,  421:  280 
    CrossrefGoogle Scholar
  • 13c Good L. Nielsen PE. Nature Biotechnol.  1998,  16:  355 
    CrossrefGoogle Scholar
  • 14a Koppelius U. Nielsen PE. Adv. Drug Delivery Rev.  2003,  55:  267 
    CrossrefGoogle Scholar
  • 14b de Koning MC. van der Marcel G. Overhand M. Curr. Opin. Chem. Biol.  2003,  7:  734 
    CrossrefGoogle Scholar
  • 15 Jacob A. Brandt O. Wuertz S. Stephan A. Schnolzer M. Hoheisel JD. Production of PNA-Arrays for Nucleic Acid Detection in Peptide Nucleic Acids   2nd ed.:  Nielsen PE. Horizon Bioscience; Wymondham, UK: 2004.  p.261-279  
    Google Scholar
  • 16 Wang J. Biosens. Bioelectron.  1998,  13:  757 
    CrossrefGoogle Scholar
  • 17a Hess A. Metzler-Nolte N. Chem. Commun.  1999,  885 
    CrossrefGoogle Scholar
  • 17b Verheijen JC. van der Marel GA. van Boom JH. Metzler-Nolte N. Bioconjugate Chem.  2000,  11:  741 
    CrossrefGoogle Scholar
  • 17c Hamzavi R. Happ T. Weitershaus K. Metzler-Nolte N. J. Organomet. Chem.  2004,  689:  4745 
    CrossrefGoogle Scholar
  • 18 Mokhir A. Stiebing R. Kraemer R. Bioorg. Med. Chem. Lett.  2003,  13:  1399 
    CrossrefGoogle Scholar
  • 19 Licandro E. Perdicchia D. Maiorana S. Baldoli C. Giannini C. Graiff C. Tiripicchio A. J. Organomet. Chem.  2003,  684:  170 ; and references cited therein
    CrossrefGoogle Scholar
  • 20 Baldoli C. Maiorana S. Licandro E. Zinzalla G. Lanfranchi M. Tiripicchio A. Tetrahedron: Asymmetry  2001,  12:  2159 ; and references cited therein
    CrossrefGoogle Scholar
  • 21 Fischer-Durand N. Salmain M. Rudolf B. Vessieres A. Zakrzewski J. Jaouen G. ChemBioChem  2004,  5:  519 ; and references cited therein
    CrossrefGoogle Scholar
  • 22 Van Staveren DR. Metzler-Nolte N. Chem. Rev.  2004,  104:  5931 
    CrossrefPubMedGoogle Scholar
  • 23a Sforza S. Galaverna G. Dossena A. Corradini R. Marchelli R. Chirality  2002,  591 
    CrossrefGoogle Scholar
  • 23b Sforza S. Haaima G. Marchelli R. Nielsen PE. Eur. J. Org. Chem.  1999,  197 
    CrossrefGoogle Scholar
  • 24 Licandro E. Maiorana S. Vandoni B. Perdicchia D. Paravidino P. Baldoli C. Synlett  2001,  757 
    Article in Thieme ConnectGoogle Scholar
  • 25 Dötz KH. Gomes da Silva E. Tetrahedron  2000,  56:  8291 
    Google Scholar
  • 26a Maiorana S. Licandro E. Capella L. Perdicchia D. Papagni A. Pure Appl. Chem.  1999,  71:  1453 
    CrossrefGoogle Scholar
  • 26b Licandro E. Maiorana S. Perdicchia D. Baldoli C. Graiff C. Tiripicchio A. J. Organomet. Chem.  2001,  617:  399 
    CrossrefGoogle Scholar
  • 27 Maiorana S. Licandro E. Perdicchia D. Baldoli C. Vandoni B. Giannini C. Salmain M. J. Mol. Cat. A: Chem.  2003,  204-205:  165 
    Google Scholar
  • 28 Menchise V. De Simone G. Tedeschi T. Corradini R. Sforza S. Marchelli R. Capasso D. Saviano M. Pedone C. Proc. Natl. Acad. Sci. U.S.A.  2003,  100:  12021 
    CrossrefGoogle Scholar
  • 29 Transition Metal Carbene Complexes   Verlag Chemie GmbH; Weinheim: 1983. 
    Google Scholar
  • 30 Haaima G. Lobse A. Buchardt O. Nielsen PE. Angew. Chem., Int. Ed. Engl.  1996,  15:  1939 
    Google Scholar
  • 32a Domling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 
    CrossrefGoogle Scholar
  • 32b Ugi I. Pure Appl. Chem.  2001,  73:  187 
    CrossrefGoogle Scholar
  • 33a Domling A. Chi KZ. Barrere M. Bioorg. Med. Chem. Lett.  1999,  9:  2871 
    Google Scholar
  • 33b Martens J. Maison W. Schlemminger I. Westerhoff O. Bioorg. Med. Chem. Lett.  2000,  8:  1343 
    Google Scholar
  • 34 Baldoli C. Maiorana S. Licandro E. Zinzalla G. Perdicchia D. Org. Lett.  2002,  4:  4341 
    CrossrefGoogle Scholar
  • 35 Davies SG. Blaggs J. Tetrahedron  1997,  41:  4463 
    Google Scholar
  • 36 Baldoli C. Giannini C. Licandro E. Maiorana S. Zinzalla G. Synlett  2004,  1044 
    Article in Thieme ConnectGoogle Scholar
  • 37a Takenaka S. Sato S. Nojima T. J. Organomet. Chem.  2004,  689:  4722 ; and references cited therein
    CrossrefGoogle Scholar
  • 37b de-los-Santos-Álvarez P. Lobo-Castañón MJ. Miranda-Ordieres AJ. Tuñón-Blanco P. Anal. Bioanal. Chem.  2004,  378:  104 
    CrossrefGoogle Scholar
  • 38 The synthesis of l-tyrosine-PNA monomer has been reported by: Puschl A. Sforza S. Haaima G. Dahl O. Nielsen PE. Tetrahedron Lett.  1998,  39:  4707 
    CrossrefGoogle Scholar
  • 39 Baldoli C. Falciola L. Licandro E. Maiorana S. Mussini P. Ramani P. Rigamonti C. Zinzalla G. J. Organomet. Chem.  2004,  689:  4791 
    CrossrefGoogle Scholar
  • 41 Baldoli C, Maiorana S, Mussini PR, and Rigamonti C. inventors; Patent MI  2004A001427. 
31

Maiorana, S. invited lecture at: ISBOMC ’04. July 14th-17th Zürich (CH) and IASOC 2004, Sept. 18th-23rd, Ischia (Italy); work to be published.

40

Baldoli, C.; Falciola, L.; Licandro, E.; Longhi, M.; Maiorana, S.; Mussini, P.; Rigamonti, C. J. Electroan. Chem., submitted.

42

Results to be published.

43

Special Issue on Transition Metal Complexes of Carbenes in 2005: J. Organomet. Chem. 2005, submitted.