Skip to main content

Bleomycin-Oligonucleotide Conjugates as Site-Specific Nucleases

  • Chapter
Artificial Nucleases

Part of the book series: Nucleic Acids and Molecular Biology ((NUCLEIC,volume 13))

  • 430 Accesses

Abstract

The idea of applying reactive oligonucleotide derivatives on nucleic acids (NA) for the purpose of achieving specific reactive effects was already suggested more than 30 years ago (Belikova et al. 1967). Since then, various oligonucleotide derivatives have been created which are capable of damaging nucleic acids and thereby influencing their function (Knorre et al. 1994). However, such oligonucleotide conjugates have not yet been applied as artificial nucleases in either scientific or medical practice. A number of drawbacks hampering a wide application of these oligonucleotide derivatives have been revealed and not yet overcome. One of these drawbacks is insufficient interaction efficiency with a target NA; another, a low selectivity of this interaction.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • van Atta RB, Bernadou J, Meunier B, Hecht SM (1990) On the chemical nature of DNA and RNA modification by a hemin model system. Biochemistry 29:4783–4789

    Article  PubMed  Google Scholar 

  • Belikova AM, Zarytova VF, Grineva NI (1967) Synthesis of ribonucleosides and diribonucleoside phosphates containing 2-chloroethylamine and nitrogen mustard residues. Tetrahedron Lett 8:3557–3562

    Article  Google Scholar 

  • Buettner GR, Moseley PL (1992) Ascorbate both activates and inactivates bleomycin by free radical generation. Biochemistry 31:9784–9788

    Article  PubMed  CAS  Google Scholar 

  • Burger RM (1998) Cleavage of nucleic acids by bleomycin. Chem Rev 98:1153–1169

    Article  PubMed  CAS  Google Scholar 

  • Burger RM, Peisach J, Horwitz SB (1982) Effect of O2 on the reactions of activated bleomycin. J Biol Chem 257:3372–3375

    PubMed  CAS  Google Scholar 

  • Chen CB, Sigman DS (1988) Sequence-specific scission of RNA by 1,10-phenanthrolinecopper linked to deoxyoligonucleotides. J Am Chem Soc 110:6570–6572

    Article  CAS  Google Scholar 

  • D’Andrea AD, Haseltine WA (1978) Sequence specific cleavage of DNA by the antitumor antibiotics neocarzinostatin and bleomycin. Proc Natl Acad Sci USA 75:3608–3612

    Article  CAS  Google Scholar 

  • Dizdaroglu M, Aruoma OI, Halliwell B (1990) Modification of bases in DNA by copper ion-l,10-phenanthroline complexes. Biochemistry 29:8447–8451

    Article  PubMed  CAS  Google Scholar 

  • Francois J-C, Saison-Behmoaras T, Barbier C, Chassignol M, Thuong NT, Helene C (1989) Sequence-specific recognition and cleavage of duplex DNA via triple-helix formation by oligonucleotides covalently linked to a phenanthroline-copper chelate. Proc Natl Acad Sci USA 86:9702–9706

    Article  PubMed  CAS  Google Scholar 

  • Frolova EI, Fedorova OS, Knorre DG (1993) Kinetic study of the addressed modification by hemin derivatives of oligonucleotides. Biochimie 75:5–11

    Article  PubMed  CAS  Google Scholar 

  • Gajewski E, Aruoma OI, Dizdaroglu M, Halliwell B (1991) Bleomycin-dependent damage to the bases in DNA is a minor side reaction. Biochemistry 30:2444–2448

    Article  PubMed  CAS  Google Scholar 

  • Giloni L, Takeshita M, Johnson F, Iden C, Grollman AP (1981) Bleomycin-induced strandscission of DNA. Mechanism of deoxyribose cleavage. J Biol Chem 256:8608–8615

    PubMed  CAS  Google Scholar 

  • Godovikova TS, Zarytova VF, Sergeyev DS (1991) Direct cleavage of a DNA fragment by bleomycin As-oligonucleotide derivative. Bioorg Khim 17:1193–1200

    PubMed  CAS  Google Scholar 

  • Hecht SM (1994) RNA degradation by bleomycin, a naturally occurring bioconjugate. Bioconjug Chem 5:513–526.

    Article  PubMed  CAS  Google Scholar 

  • Hecht SM (2000) Bleomycin: new perspectives on the mechanism of action. J Nat Prod 63:158–168

    Article  PubMed  CAS  Google Scholar 

  • Henichart JP, Bernier JL, Helbecque N, Houssin R (1985) Is the bithiazole moiety of bleomycin a classical intercalator? Nucleic Acids Res 13:6703–6717

    Article  PubMed  CAS  Google Scholar 

  • Holmes CE, Hecht SM (1993) Fe-Bleomycin cleaves a transfer RNA precursor and its “transfer-DNA” analog at the same major site. J Biol Chem 268:25909–25913

    Google Scholar 

  • Holmes SE, Carter BJ, Hecht SM (1993) Characterization of iron(II)-bleomycin-mediated RNA strand scission. Biochemistry 32:4293–4307.

    Article  PubMed  CAS  Google Scholar 

  • Holmes SE, Abraham AT, Hecht SM, Florentz C, Giege R (1996) Fe-Bleomycin as a probe of RNA conformation. Nucleic Acids Res 24:3399–3406

    Article  PubMed  CAS  Google Scholar 

  • Holmes SE, Duff RJ, van der Marel GA, van Boom J, Hecht SM (1997) On the chemistry of RNA degradation by Fe-bleomycin. Bioorg Med Chem 5:1235–1248.

    Article  PubMed  CAS  Google Scholar 

  • Keck MV, Hecht SM (1995) Sequence-specific hydrolysis of yeast tRNA(Phe) mediated by metal-free bleomycin. Biochemistry 34:12029–12037

    Article  PubMed  CAS  Google Scholar 

  • Knorre DG, Vlassov VV, Zarytova VF, Lebedev AV, Fedorova OS (1994) Design and targeted reactions of oligonucleotide derivatives. CRC Press, Boca Raton

    Google Scholar 

  • Kuramoshi H, Takahashi K, Takita T, Umezawa H (1981) An active intermediate formed in the reaction of bleomycin-Fe(II) complex with oxygen. J Antibiot 34:576–582

    Article  Google Scholar 

  • Kutyavin IV, Podyminogin MA, Bazhina YN, Fedorova OS, Knorre DG, Levina AS, Mamaev SV, Zarytova VF (1988) N-(2-hydroxyethyl)phenazinium derivatives of oligonucleotides as effectors of the sequence-specific modification of nucleic acids with reactive oligonucleotide derivatives.FEBS Lett 238:35–38

    Article  PubMed  CAS  Google Scholar 

  • Lin SB, Blake KR, Miller PS, Ts’o PO (1989) Use of EDTA derivatization to characterize interactions between oligodeoxyribonucleoside methylphosphonates and nucleic acids. Biochemistry 28:1054–1061

    Article  PubMed  CAS  Google Scholar 

  • Lown JW, Sim S-K (1977) The mechanism of the bleomycin induced cleavage of DNA. Biochem Biophys Res Commun 77:1150–1157

    Article  PubMed  CAS  Google Scholar 

  • Magliozzo RS, Peisach S, Ciriolo MR (1989) Transfer RNA is cleaved by activated bleomycin. Mol Pharmacol 35:428–432

    PubMed  CAS  Google Scholar 

  • Mir LM, Tounekti O, Orlowski S (1996) Bleomycin: revival of an old drug. Gen Pharmacol 27:745–748

    Article  PubMed  CAS  Google Scholar 

  • Murugesan N, Xu C, Ehrenfeld GM, Sugiyama H, Kilkuskie RE, Rodriguez LO, Chang LH, Hecht SM (1985) Analysis of products formed during bleomycin-mediated DNA degradation. Biochemistry 24:5735–5744

    Article  PubMed  CAS  Google Scholar 

  • Onishi T, Iwata H, Takagi Y (1975) Effects of reducing and oxidizing agents on the action of bleomycin. J Biochem 77:745–752

    PubMed  CAS  Google Scholar 

  • Otsuka M, Masuda T, Haupt A, Ohno M, Shiraki T, Sugiura Y, Maeda K (1990) Mandesigned bleomycin with altered sequence specificity in DNA cleavage. J Am Chem Soc 112:838–845

    Article  CAS  Google Scholar 

  • Povirk LF (1979) Catalytic release of deoxyribonucleic acid by oxidation and reduction of an iron-bleomycin complex. Biochemistry 18:3989–3995

    Article  PubMed  CAS  Google Scholar 

  • Rabow LE, McGall GH, Stubbe J, Kozarich JW (1990) Identification of the source of oxygen in the alkaline-labile product accompanying cytosine release during bleomycinmediated oxidative degradation of d(CGCGCG). J Am Chem Soc 112:3203–3208

    Article  CAS  Google Scholar 

  • Sam JW, Tang X-J, Peisach J (1994) Electrospray mass spectrometry of iron bleomycin: demonstration that activated bleomycin is a ferric peroxide complex. J Am Chem Soc 116:5250–5256

    Article  CAS  Google Scholar 

  • Sausville EA, Peisach J, Horwitz SB (1978) The effect of chelating agents and metal ions on the degradation of DNA by bleomycin. Biochemistry 17:2740–2746

    Article  PubMed  CAS  Google Scholar 

  • Sergeyev DS, Zarytova VF (1996) Interaction of bleomycin and its oligonucleotide derivatives with nucleic acids. Russ Chem Rev 65:355–378

    Article  Google Scholar 

  • Sergeyev DS, Zarytova VF, Mamaev SV, Godovikova TS, Vlassov VV (1992) Sequences-pecific cleavage of single-stranded DNA by oligonucleotides conjugated to bleomycin. Antisense Res Dev 2:235–241

    Google Scholar 

  • Sergeyev DS, Godovikova TS, Zarytova VF (1995a) Catalytic site-specific cleavage of a DNA-target by an oligonucleotide carrying bleomycin As. Nucleic Acids Res 23:4400–4406

    Article  PubMed  CAS  Google Scholar 

  • Sergeyev DS, Godovikova TS, Zarytova VF (1995b) Cleavage of double-strand DNA by bleomycin derivatives of oligonucleotides forming a ternary complex. Bioorg Khim 21:188–196

    Google Scholar 

  • Sergeyev DS, Denisov AY, Zarytova VF (1996) Structure elucidation of an oligonucleotide derivative of bleomycin As by l3C NMR. Bioorg Khim 22:54–57

    Google Scholar 

  • Sersa G, Cufer T, Cemazar M, Rebersek M, Zvonimir R (2000) Electrochemotherapy with bleomycin in the treatment of hypernephroma metastasis: case report and literature review. Tumori 86:163–165

    PubMed  CAS  Google Scholar 

  • Smith JB, Vorobjev PE, Zarytova VF, Wickstrom E (1999) Site-specific cleavage of RNA by antisense DNA-bleomycin As conjugate. American Association for Cancer Research, Annual Meeting,1O-14 April, Philadelphia, PA, 133 pp

    Google Scholar 

  • Strobel SA, Dervan PB (1990) Site-specific cleavage of a yeast chromosome by oligonucleotide-directed triple-helix formation. Science 249:73–75.

    Article  PubMed  CAS  Google Scholar 

  • Stubbe J, Kozarich JW (1987) Mechanism of bleomycin-induced DNA degradation. Chem Rev 87:1107–1136

    Article  CAS  Google Scholar 

  • Sugiyama H, Kilkuskie RE, Chang LH, Ma LT, Hecht SM (1986) DNA strand scission by bleomycin: catalytic cleavage and strand selectivity. J Am Chem Soc 108:3852–3854

    Article  CAS  Google Scholar 

  • Takita T, Fujii A, Fukuoka T, Umezawa H (1973) Chemical cleavage of bleomycin to bleomycinic acid and synthesis of new bleomycins. J Antibiot 26:252–254

    Article  PubMed  CAS  Google Scholar 

  • Umezawa H (1976) Structure and action of bleomycin. Prog Biochem Pharmacol 11:18–27

    PubMed  CAS  Google Scholar 

  • Umezawa H (1984) Antitumor antibiotics and low molecular weight immunomodifiers of microbial origin. Cancer Treat Rep 68:137–144

    PubMed  CAS  Google Scholar 

  • Umezawa H, Maeda K, Takeushi T, Okami Y (1966) New antibiotics, bleomycinsA and B. J Antibiot 19:200–209

    PubMed  CAS  Google Scholar 

  • Vlassov VV, Zarytova VF, Kutiavin IV, Mamaev SV, Podyminogin MA (1986) Complementary addressed modification and cleavage of a single stranded DNA fragment with alkylating oligonucleotide derivatives. Nucleic Acids Res 14:4065–4076

    Article  PubMed  CAS  Google Scholar 

  • Vorobjev PE, Markushin YY, Sergeyev DS, Zarytova VF (1996) Effector oligonucleotides increase efficiency of site-specific cleavage of target DNA by bleomycin derivative of tetranucleotide. Bioorg Khim 22:111–116

    Google Scholar 

  • Vorobjev PE, Yapryntseva OV, Zarytova VF (2000) Catalytic cleavage of DNA by bleomycin-oligonucleotide conjugates. Millennium Conference on Nucleic acid therapeutics, 8-11 January, Florida, p 40

    Google Scholar 

  • Vorobjev PE, Pyshnaya IA, Wickstrom E, Zarytova VF (2002) Directed cleavage of RNA within an imperfect complementary complex by oligonucleotide-bleomycin As conjugates. Russ Chem Bull Int Ed 51:51:1187–1189

    Article  CAS  Google Scholar 

  • Vorobjev P, Yapryntseva O, Chaika O, Pyshnaya I, Wickstrom E, Zarytova V (2002) The design of bleomycin-oligonucleotide conjugates for efficient cleavage of nucleic acids. XV International round table “Nucleosides, nucleotides and nucleic acids”. Leuven, Belgium, September 10-14, P 203

    Google Scholar 

  • Watanabe M, Takabe Y, Katsumata T, Terasima T, Umezawa H. (1973) Response in macromolecular syntheses of mouse L cell to bleomycin, with special reference to cellantibiotic interaction. J Antibiot 26:417–423

    Article  PubMed  CAS  Google Scholar 

  • Worth LJ, Frank BL, Christner DA, Absalon MJ, Stubbe J, Kozarich JW (1993) Isotope effects on the cleavage of DNA by bleomycin: mechanism and modulation. Biochemistry 32:2601–2609

    Article  PubMed  CAS  Google Scholar 

  • Wu JC, Kozarich JW, Stubbe (1983) The mechanism of free base formation from DNA by bleomycin. A proposal based on site specific tritium release from poly(dA-dU). J Biol Chem 258:4694–4697

    PubMed  CAS  Google Scholar 

  • Wu JC, Kozarich JW, Stubbe J (1985) Mechanism of bleomycin: evidence for a rate-determining 4′-hydrogen abstraction from poly(dA-dU) associated with the formation of both free base and base propenal. Biochemistry 24:7562–7568

    Article  PubMed  CAS  Google Scholar 

  • Yamazaki ZI, Muller WEG, Zahn RK (1973) Action of bleomycin on programmed synthesis. Influence on enzymatic DNA, RNA and protein synthesis. Biochim Biophys Acta 308:412–421

    Article  PubMed  CAS  Google Scholar 

  • Zarytova VF, Godovikova TS, Kutyavin IV, Khalimskaya LM (1987) Reactive oligonucleotide derivatives as affinity reagents and probes in molecular biology. In: Bruzik KS, Stec WJ (eds) Biophosphates and their analogues — synthesis, structure, metabolism and activity. Elsevier, Amsterdam, pp 149–164

    Google Scholar 

  • Zarytova VF, Sergeyev DS, Godovikova TS (1993) Synthesis of bleomycin As oligonucleotide derivatives and site-specific cleavage of the DNA target. Bioconjugate Chem 4:189–193

    Article  CAS  Google Scholar 

  • Zarytova V, Ivanova E, Venyaminova A (1998) Design of functional diversity in oligonucleotides via zwitter-ionic derivatives of deprotected oligonucleotides. Nucleosides Nucleotides 17:649–662

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Vorobjev, P.E., Zarytova, V.F. (2004). Bleomycin-Oligonucleotide Conjugates as Site-Specific Nucleases. In: Zenkova, M.A. (eds) Artificial Nucleases. Nucleic Acids and Molecular Biology, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18510-6_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-18510-6_15

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62139-0

  • Online ISBN: 978-3-642-18510-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics