DEPARTMENT OF NUCLEIC ACID CHEMISTRYInstitute of Organic Chemistry and Biochemistry, Prague, Czech Republic Group of Nucleic Acid Chemistry (A. Holý)Group of Biochemistry of Antimetabolites (I. Votruba) |
Chemistry of nucleic acids is a traditional and continuously developing topics of this Institute. The Department formed in the 60's around the group of scientists who studied the chemistry of the nucleobases, nucleosides and oligonucleotides and made principal contribution to the development in this field. Outstanding achievements of the past encompass original studies on 6-azapyrimidines and 5-azapyrimidines and their nucleosides which resulted in the discovery of potent antimetabolites (6-azauridine, 2'-deoxy-5-azacytidine), fundamental investigation on the mechanisms of nucleosidation reactions, sugar-modified nucleosides and transformation of nucleoside molecules. In the oligonucleotide chemistry, methods of chemical and enzymatic oligoribonucleotide synthesis were developed in this Laboratory.Research in this Department traditionally combines development of novel biologically active compounds with the investigation of their metabolism and mode of action. It is based upon numerous joint investigations of different subjects in medicine: immunology, virology (studies on retroviruses, DNA viruses), antitumor and antileukemic studies, etc., both in- and outside the country. The tissue culture laboratory run by the Department performs the screening of the cytostatic activity in vitro. The present research in the Department concerns mainly the design and synthesis of analogues of nucleic acid components including modified nucleobases, nucleosides with modified sugar moiety, nucleotides with modified phosphomonoester linkage (acyclic nucleoside phosphonate analogues, ANP) and oligonucleotides with modified internucleotidic linkage, isolation of target enzymes, transport and metabolism studies of active compounds. |