1 Alexandre S. BOUTORINE Curriculum Vitae Born: March 3, 1951 in Novosibirsk, URSS (Russia) Nationality: Russian. Martial Status: Married, 2 children. Personal address: 2 rue René Cassin, 91700 Sainte Geneviève des Bois, France Native language: Russian. Foreign languages: English, French (fluently) and Polish (reading and speaking) Correspondence address: Scientific Unity "Regulation and Dynamics of Genomes", INSERM U 565 - CNRS UMR 7196, Department "Regulations, Development and Molecular Diversity", National Museum of natural History, 57 rue Cuvier, C.P. 26, 75231 Paris cedex 05 FRANCE, tel. +33-1-40.79.36.96, fax. +33-1-40.79.37.05, E.mail: alexandre.boutorine@mnhn.fr Education and Degrees: 1968 - 1973 - Chemical Department, Faculty of Natural Sciences (physical and biological chemistry), Novosibirsk State University, Novosibirsk, USSR (Russia). Ph. D. degree (Candidate of Chemical Sciences) obtained at the M.V. Lomonosov Moscow State University, Moscow, USSR (Russia), October 13, 1978. Other diplomas and attestations: -Inscription for the French national qualification list of University Professors, specialty: “Biochemistry and molecular biology”, March 22, 1993. -Inscription for the French national qualification list of Professors of National Museum of Natural History, specialty: “Biochemistry and molecular biology”, March 15, 1994. Membership in scientific societies: Member of International Society for Nucleosides, Nucleotides and Nucleic Acids (IS3NA). Professional experience: September 1973 – September 1975 - Probation Researcher, Institute of Organic Chemistry, Siberian Division of the USSR Academy of Sciences, Novosibirsk, USSR. September 1975 – April 1983 - Scientific Researcher (1975 - 1976), then Director of the Nucleic Acids Research Laboratory, Institute of Molecular Biology, Scientific Center "Vector", USSR Ministry of the Medical Industry, Kol'tsovo, Novosibirsk Region, USSR. October 1979 - June 1980 - post-doctoral Researcher, Laboratory of Biochemistry, Institute of Molecular and Cellular Biology of CNRS, Strasbourg, France. 2 April 1983 – September 1992 - Senior Scientific Researcher, Institute of Bioorganic Chemistry, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia. April 1989 - October 1990 - post-doctoral Researcher, Laboratory of Biophysics, National Museum of the Natural History, CNRS URA481 - INSERM U201, Paris, France. August 1992 - January 1993 - Invited Professor, Laboratory of Biophysics, National Museum of the Natural History, CNRS URA481 - INSERM U201, Paris, France. January 1993 - January 1995 - Allocated Researcher of CNRS, Fellowship of French National Agency for the AIDS Research, in the same Laboratory. January 1995 - October 1996 - Senior Research Engineer, Genta Pharmaceuticals Europe, Marseilles, France 1 December 1996 - present time - Professor 2nd class, Department "Regulations, Development and Molecular Diversity", National Museum of the Natural History, Paris, France. Field of Scientific Interests: Chemical modification of the biopolymers: nucleic acids, proteins. Chemistry of nucleic acids. Synthesis of chemical conjugates of oligonucleotides with intercalating, hydrophobic, catalytic, chemically and photochemically active molecules. Studies of nucleic acid - protein interactions by the chemical and enzymatic methods. Studies of interactions of the oligonucleotide derivatives with other biopolymers and living cells. Application of modified oligonucleotides for gene expression researches. Studies of the stability of nucleic acids derivatives in the biological media and of mechanisms of their penetration into the living cells. Studies of DNA-ligand interactions. Synthesis and physico-chemical studies of ligands recognizing double-stranded DNA in a native state: triplex-forming oligonucleotides, minor groove binders of polyamide type. Fluorescent and radioactive labeling of biopolymers and ligands. Professional skills: Chemical organic synthesis. Synthesis of nucleic acid conjugates and oligocarboxamide minor groove binders. Chemical modification of proteins, nucleic acids and oligonucleotides. Kinetic methods of studies. Studies of DNA-protein and DNA-ligand interactions. Physico-chemical and spectroscopic methods of studies. Isolation and purification of nucleic acids, proteins and other biologically active molecules. All types of liquid chromatography and gel-electrophoresis. Conventional chromatography, HPLC, electrophoresis, UV and visible spectroscopy. Analytical methods of nucleic acids research. 3 Radiochemistry. Radioactive labeling of nucleic acids and oligonucleotides, isolation, purification and use of labeled compounds. Fluorescent labeling of nucleic acids and proteins. Fluorescent labeling. Synthesis of fluorescent biological conjugates. Enzymatic methods of nucleic acids research. Cell-free enzymatic systems (transcription, translation, PCR, etc.). Cell cultures. Visible and fluorescent microscopy. Selected publications (2004-2010): 1. RYABININ V.A., BOUTORINE A.S., HÉLÈNE C., PYSHNYI D.V., SINYAKOV A.N. Oligonucleotide - minor groove binder conjugates and their complexes with complementary DNA: effect of conjugate structural factors on the thermal stability of duplexes", Nucleosides, Nucleotides and Nucleic Acids (2004) v. 23, n. 5, p. 789-804. 2. RYABININ V.A., BOUTORINE A.S., HÉLÈNE C., DENISOV A.Yu., PYSHNYI D.V., SINYAKOV A.N. Oligonucleotide - Minor Groove Binder 1:2 Conjugates: Side by Side Parallel Minor Groove Binder Motif in Stabilisation of DNA Duplex Nucleosides, Nucleotides and Nucleic Acids (2004) v. 23, n. 6-7, pp. 953-968. 3. GOSSE C., BOUTORINE A., AUJARD I., CHAMI M., KONONOV A., COGNÉLAAGE E., ALLEMAND J.-F., LI J., JULLIEN L. Micelles of lipid-oligonucleotide conjugates: Implicatios for membrane anchoring and base pairing" J. Phys. Chem. B. (2004) v. 108, n. 20, 6485-6497. 4. NOVOPASHINA D.S., SINYAKOV A.N., RYABININ V.A., VENYAMINOVA A.G., PERROUAULT L., BRUNET E., GIOVNNANGELI C., BOUTORINE A.S. Binding properties of the conjugates of oligo(2’-O-methylribonucleotides) with minor groove binders targeted to double-stranded DNA, Nucleosides, Nucleotides and Nucleic Acids (2004) v. 23, n. 6-7, 1015-1022. 5. BOUTORINE A.S., ARIMONDO P.B.. Sequence-Specific Cleavage of Double-stranded DNA. Artificial Nucleases, in: Nucleic Acids and Molecular Biology, M. Zenkova, ed., Springer-Verlag, Berlin – Heidelberg, 2004, v.13, p. 243-268 6. BOUTORINE A.S., SUN J.S.. Post-synthetic functionalization of triple helix-forming oligonucleotides (Chapter 15 "Oligonucleotide Synthesis: Methods and Applications"). P. Herdewijn, ed, in: Methods in Molecular Biology, 2005, v. 288, p. 251-260. 7. SINYAKOV A.N., BOUTORINE A.S., HÉLÈNE C., RYABININ V.A. Stabilization of GC-containing duplexes by polyamides with parallel orientation in minor groove. 4 Russ.J. Bioorgan. Chem. (2004) v. 30, n. 5, pp. 502-504. 8. DA ROS T., SPALLUTO G., PRATO M., SAISON-BEHMOARAS T., BOUTORINE A., CACCIARI B. Oligonucleotides and Oligonucleotide Conjugates: A New Approach for Cancer Treatment. Current Medicinal Chemistry (2005) v. 12, n. 1, 71-88. 9. RYABININ V.A., BOUTORINE A.S., HÉLÈNE C., DENISOV A.Yu., PYSHNYI D.V., SINYAKOV A.N. Effect of structural factors on the stability of duplexes formed by oligonucleotide conjugates with minor groove binder conjugates. Russ.J. Bioorgan. Chem (2005) v. 31, n. 2, 146 – 152 (Russian version p. 159 – 166). 10. ARIMONDO P.B., LACO G.S., THOMAS C.J., HALBY L., PEZ D., SCHMITT P., BOUTORINE A., GARESTIER T., POMMIER Y., HECHT S.M., SUN J.S., BAILLY C. Activation of camptothecin derivatives by conjugation to triple helix-forming oligonucleotides Biochemistry (2005,) v. 44, n. 11, 4171-4180 11. HALBY L., RYABININ V.A., SINYAKOV A.N., BOUTORINE A.S. Functionalized Head-to-head Hairpin Polyamides: Synthesis, Double Stranded DNA Binding Activity and Affinity Bioorganic and Medicinal Chemistry Letters (2005) v. 15, n. 16, 3720-3724 12. NOVOPASHINA D.S., SINYAKOV A.N., RYABININ V.A., VENYAMINOVA A.G., HALBY L., SUN J.S., BOUTORINE A.S. Sequence-specific Conjugates of Oligo(2'-O-methylribonucleotides) and Hairpin Oligocarboxamide Minor Groove Binders: Design, Synthesis and dsDNA Binding Studies Chemistry and Biodiversity (2005) v. 2, n. 7, 936 – 952. 13. HALBY L., RYABININ V.A., SINYAKOV A.N., NOVOPASHINA D.S., VENYAMINOVA A.G., GROKHOVSKY S.L., SUROVAYA A.N., GURSKY G.V., BOUTORINE A.S. Head-to-head bis-Hairpin Polyamide Minor Groove Binders and Their Conjugates with Triplex-forming Oligonucleotides: Studies of Interaction with Target Doublestranded DNA. J Biomol. Struct. Dynam. (2007), v. 25, n. 1, 61-76 14. BOUTORINE A.S., ESCUDÉ C. Biophysical Analysis of Triple Helix Formation Current Protocols in Nucleic Acid Chemistry (2007), UNIT 7.12 Biophysical Analysis of Triple-Helix Formation, John Wiley & Sons, Inc. 15. SIMON P., CANNATA F., PERROUAULT L., HALBY L., CONCORDET J.P., BOUTORINE A., RYABININ V., SINYAKOV A., GIOVANNANGELI C. Sequence-specific DNA cleavage mediated by bipyridine polyamide conjugates Nucleic Acids Research (2008), Vol. 36, No. 11, 3531–3538 5 16. TERRIER P., BOUTORINE A., HALBY L., DE PAUW E., TORTAJADA J., BUCHMANN W.: Complexes non-covalents ADN/polymères et spectrométrie de masse, Spectra Analyse (2008), n° 264, pp. 36 – 40. 17. VEKHOFF P., HALBY L., OUSSEDIK K., DALLAVALLE S., MERLINI L., MAHIEU C., LANSIAUX A., BAILLY C., BOUTORINE A., PISANO C., GIANNINI G., ALLOATTI D., ARIMONDO P. Optimized synthesis and reinforced efficacy of novel triplex-forming camptothecin derivatives based on gimatecan, Bioconjugate Chemistry (2009), vol. 20 (4), pp 666–672. 18. BUCHMANN W., BOUTORINE A., HALBY L., TORTAJADA J., DE PAUW E. A new method for the determination of the relative affinity of a ligand against various DNA sequences by electrospray ionization mass spectrometry. Application to a polyamide minor groove binder. J. Mass Spectr., 2009, Vol. 44 (8), pp. 1171-1181 19. BOUTORINE A.S., DOLUCA O., FILICHEV V.V. Optimization of the sequence of twisted intercalating nucleic acids (TINA) forming triple helix with the polypurine tract of the proviral HIV DNA Nucl. Acids Symp. Ser., 2009, Vol. 53, pp. 139-140.