Group of Nucleic Acid Chemistry

DEPARTMENT OF NUCLEIC ACID CHEMISTRY
Institute of Organic Chemistry and Biochemistry, Prague, Czech Republic

RNDr. Antonín Holý D.Sc., Dr.h.c.

[A.Holy]

Born September 1, 1936 in Prague

1954 - 1959Faculty of Sciences, Charles University, Prague, graduated in organic chemistry.
1960 - 1963Ph.D. study at the Institute of Organic Chemistry and Biochemistry, in organic chemistry. Dissertation: "Application of Vilsmeier-Haack reaction in Aliphatic Chemistry".
1963 - now research scientist, Institute of Organic Chemistry and Biochemistry, Prague
1967senior scientist
1983Head of nucleic acid chemistry group
1984Doctor of Sciences (D.Sc.), dissertation: "Nucleoside and Nucleotide Analogs: Synthesis and Biological Activity".
1987Head of department Bioorganic Chemistry
1988elected Corresponding Member of Czechoslovak Academy of Sciences (which was dissolved by Jan.1, 1993).
1990Member of the Scientific Council of the Czech Academy of Sciences.
1992 - 1994Deputy Director for Research
1994 - 2002Director of the Institute

Honors and Prizes:

1986Czechoslovak National Prize for Chemistry "Acyclic Nucleoside and Nucleotide Analogs".
1998Honor plaque: Nucleic Acids Chemistry journal.
1999Honor medal, Czech Chemical Society
Doctor honoris causa, Palacký University, Olomouc
2001Descartes Prize, European Union
2002Elion Award of International Society for Antiviral Research
2002State Medal "Pour merit"
Membership in Editorial Boards:
Nucleic Acids Chemistry (finished)
Nucleosides and Nucleotides
Antiviral Research
International Journal of Purine and Pyrimidine Research
Antiviral Chemistry and Chemotherapy
ChemBioChem
Elected scientific functions:
Vice-Chairman, Scientific Council of the Academy of Sciences of the Czech Republic,
Member of Scientific Board, Faculty of Sciences, Charles University Prague
Publications:
>450 original papers, 60 patent applications.
Books: coauthorship in:
Synthetic Procedures in Nucleic Acid Chemistry (W.W.Zorbach, R.S.Tipson,Eds.), Interscience 1968.
Nucleic Acid Chemistry (L.B.Townsend, R.S.Tipson,Eds.), Wiley-Interscience 1978.
Approaches to Antiviral Agents (M.R.Harnden,Ed.), Macmillan, 1985.
Nucleotide Analogues as Antiviral Agents (J.C.Martin,Ed.), ACS 1989.
Advances in Antiviral Drug Research (E.De Clercq, Ed.), JAI Press 1993.
Antibiotics and Antiviral Compounds (K.Krohn Ed.), Verlag Chemie 1993.
Recent Advances in Nucleosides: Chemistry and Chemotherapy (C.K.Chu, Ed.), Elsevier, 2002.
Areas of scientific interest:
nucleic acid chemistry - sugar-modified nucleoside analogs, phosphorus-modified nucleotide analogs; enzymes of nucleic acids metabolism: specificity & inhibitors of enzymes, virus-specific enzymes; biological applications of modified nucleic acids components: antivirals, cytostatics, antiparasitic drugs; anti-AIDS drugs; drug development.
Scientific organisatory activity:
organizer of a serial "Symposium on the Chemistry of Nucleic Acids Components" which is taking place from 1969 in three-year-intervals in Czechoslovakia/Czech Republic (12th symposium of this series took place in 2002).
Educational activity:
During the scientific career 7 Ph.D.'s, two long-term students, nine long-term visiting scientists (USA, Canada, Germany, Japan, Russia, Poland, Bulgaria), four diploma students. At present, three Ph.D. students, 1 diploma student.
Teaching: special lecture "Principles of antimetabolites for design of cytostatics and antivirals" (full-term lecture, 22 hours): Faculty of Science, Charles University Prague (from 1998), dtto Faculty of Science, Palacký University Olomouc (from 1999). Lectures on antivirals in Faculty of Medicine, Charles University, Prague, School of Pharmacy, Brno, Faculty of Medicine, Olomouc.
Realization of Research Results:
  • Duviragel™ (antiherpeticum), marketed by Léčiva Praha (Czech Republic) (1984)
  • original procedures for preparation of azidothymidine (anti-AIDS drug), produced in LACHEMA Brno (Czech Republic)
  • original antiviral drugs developed in USA by Gilead Sciences
    • Vistide™ (cidofovir) approved and marketed in USA a EU (1996) against CMV retinitis, also used fo treatment of malignizing papillomatoses, anogenital herpes, active against smallpox, monkeypox, etc.
    • Viread™ (tenofovir disoproxil) - novel anti-AIDS drug, approved 2001
    • Hepsera™ (adefovir dipivoxil) - novel drug against hepatitis B, approved 2002
International response:
Research in the field of acyclic nucleoside and nucleotide analogues opened new field in the development of antivirals and cytostatics. Adopted by numerous academical and industrial research laboratories: during the last 15 years 1140 original scientific papers.
International collaboration:
joint research with groups in USA, Belgium, Germany, Switzerland.
Languages:
English, German, Russian.
Selected scientific papers:
1998-2002
Present research projects:
  • structure-activity relationship in the field of acyclic nucleotide phosphonates (ANP); search for novel base- and chain-modified antiviral and anticancer ANP derivatives & their mode of action, novel synthetic methods for ANP preparation
  • ring-open ANP - synthetic approaches, mechanism of action
  • ANP prodrugs, effect of increased cellular drug uptake
  • immunomodulatory activity of ANP - effect of substitution upon stimulation of cytokines and activity of macrophages
  • metal complex formation of base-modified ANP
Present project funding:
  • Programme of targeted projects, Academy of Sciences of the Czech Republic
  • grants of the State Grant Agency (three shared grants)
  • two COST projects (# 13.40, # 20.002)
  • Descartes Prize (2002-2004)
Contact:
RNDr.A.Holý, DrSc.
Institute of Organic Chemistry and Biochemistry
Flemingovo nám.2
CZ-166 10 Praha 6 Dejvice
Phone: +420-220183-384, +420-220183-262
Fax: +420-220183-560
E-mail: holy@uochb.cas.cz