LABORATORY OF NUCLEOSIDE CHEMISTRY
Head: Jerzy Boryski
Research Staff:
Daniel Baranowski, Joanna Fogt, Grzegorz Framski, Zofia Jahnz-Wechmann, Piotr Januszczyk, Tomasz Ostrowski, Joanna Zeidler
Research Support:
Zofia Adamska, Krystyna Lembicz
Ph.D. Students:
Anna Krajczyk
Keywords:
synthesis of nucleoside analogs, transglycosylation, glycosylic bond stability, antivirals, structure-activity relationships
The research is concentrated upon the synthesis of modified nucleobases, nucleosides and nucleotides together with the study on their structural features, chemical properties and biological activities. The main objects of interest are nucleoside analogs designed to mimic the natural substrates for: i) probing the structural and steric requirements of selected enzymes, ii) enhancing the specificity in enzyme inhibition, iii) developing new antiviral and anticancer agents. Studies in the field of synthesis and reactivity of nitrogen heterocycles also include the stability, solubility and transport characteristics important for the desired activity in vivo of the aforementioned analogs.
Current research activities:
- search for new approaches towards synthesis of nucleobases and nucleosides (controlled degradation, rearrangements);
- selective alkylation and aralkylation of nucleosides and nucleotides;
- synthesis and characterization of nucleoside analogs that are potentially and actually biologically active, mainly ring analogs of pyrimidine and purine, acyclonucleosides, 2’-C-alkylribofuranosides, and 2’,3’-dideoxynucleosides;
- attempts to define structure-activity relationships in base-modified acyclovir and gan-ciclovir analogs;
- synthesis and characterization of conformationally restricted nucleosides;
- study on the mechanism and applications of transglycosylation reactions in the nucleoside chemistry;
- determination of the structural factors influencing the stability of N-glycosylic bonds;
- reaction of partial acylation of the 2’,3’-cis-diol system in the ribofuranosyl and 2’-C-alkylribofuranosyl nucleoside series;
- study on glycosylation reactions of naturally occurring poliphenolic compounds and biological activity of their sugar conjugates.
SELECTED PUBLICATIONS
T. Ostrowski, B. Golankiewicz, E. De Clercq, J. Balzarini
Synthesis and biological activity of tricyclic analogues of 9-{[cis-1’,2’-bis(hydroxy-methyl)-cycloprop-1’-yl]methyl}guanine
Bioorgan. Med. Chem. 14, 3535-3542 (2006).
A. Szymańska, M. Szymczak, J. Boryski, J. Stawiński, A. Kraszewski, G. Gollu, G. Sanna, G. Gilberti, R. Loddo, P. La Colla
Aryl nucleoside H-phosphonates. Part 15: Synthesis, properties and anti-HIV activity of aryl nucleoside 5’-α-hydroxyphosphonates
Bioorgan. Med. Chem. 14, 1924-1934 (2006).
B. Golankiewicz, T. Ostrowski
Tricyclic nucleoside analogues as antiherpes agent.
Antiviral Res. 71, 134-140 (2006).
G. Wenska, J. Koput, T. Pędziński, B. Marciniak, J. Karolczak, B. Golankiewicz
Effect of Hydroxylic Solvent on the Fluorescence Behavior of Some Bioactive 9-Oxoimidazo[1,2-a]purine Derivatives
J. Phys. Chem. 110, 11025-11033 (2006).
G. Framski, Z. Gdaniec, M. Gdaniec, J. Boryski
A reinvestigated mechanism of ribosylation of adenine under silylating conditions
Tetrahedron 62, 10123-10129 (2006).
I. Łakomska, M. Barwiołek, E. Szłyk, B. Golankiewicz
Synthesis and spectroscopic characterization of palladium(II) complexes with 6,8-dimethylimidazo[1,5-a]-1,3,5-triazin-4(3H)-one and 6,8-dimethyl-2-thioxo-2,3-dihydroimidazo-[1,5-a]-1,3,5-triazin-4(1H)-one
Trans. Metal Chem. 32, 70-73 (2007).
Z. Jahnz-Wechmann, J. Boryski, K. Izawa, T. Onishi, J. Neyts, E. De Clercq
New Analogs of Acyclovir Substituted at the Side Chain
Nucleos. Nucleot. Nucleic Acids 26, 917-920 (2007).
J. Boryski
Reactions of Transglycosylation in the Nucleoside Chemistry
Current Org. Chem. 12, 309-325 (2008).
J. Fogt, P. Januszczyk, G. Framski, T. Onishi, K. Izawa, E. De Clercq, J. Neyts, J. Boryski
Synthesis and antiviral activity of novel derivatives of 2'-β-C-methylcytidine
Nucleic Acids Symposium Series No. 52, 605-606 (2008).
T. Ostrowski, J. Zeidler
Synthesis of 5-ethynyl-β-D-ribofuranosyl-1H-[1,2,3]trazole-4-carboxylic acid amide (isosteric to EICAR) and its derivatives
Nucleic Acids Symposium Series No. 52, 585-586 (2008).
G. Grynkiewicz, W. Szeja and J. Boryski
Synthetic analogs of natural glycosides in drug discovery and development.
Acta Poloniae Pharmaceutica – Drug Research, 65, 655-676 (2008).
J. Fogt, P. Januszczyk, T. Onishi, K. Izawa, and J. Boryski
Partial acylation of cytidine and its 2’-C-methyl analogue as a tool to functionalize the ribonucleosidic 2’,3’-cis-diol system.
ARKIVOC, 198-205 (2009).
J. Romanowska, A. Szymańska-Michalak, J. Boryski, J. Stawiński, A. Kraszewski, R. Loddo, G. Sanna, G. Collu, G. Gilberti, B. Secci, P. La Colla
Aryl nucleoside H-phosphonates. Part 16: Synthesis and anti-HIV-1 activity of di-aryl nucleoside phosphotriesters.
Bioorganic & Medicinal Chemistry, 17, 3489-3498 (2009).
T. Ostrowski, B. Golankiewicz, E. De Clercq, G. Andrei, R. Snoeck
Synthesis and anti VZV activity of 6-heteroaryl derivatives of tricyclic acyclovir and
9-{[cis-1’,2’-bis(hydroxymethyl)-cycloprop-1’-yl]methyl}guanine analogues.
Eur. J. Med. Chem., 44, 3313-3317 (2009).
P. Januszczyk, J. Fogt, J. Boryski, K. Izawa, T. Onishi, J. Neyts, E. De Clercq
Synthesis and Antiviral Evaluation of 2’-C-Methyl Analogues of 5-Alkynyl- and
6-Alkylfurano- and Pyrrolo[2,3-d]pyrimidine Ribonucleosides.
Nucleosides, Nucleotides and Nucleic Acids, 28, 713-723, (2009).
P. Zawadzki, G. Ślósarek, J. Boryski, P. Wojtaszek
A correlation fluorescence spectroscopy study of ligand interaction with cytokinin-specific binding protein from mung bean.
Biol. Chem., 391, (2010).