Open AccessAntisense oligodeoxynucleotides: useful tool for search and assessment of new targets for anti-malarial drugs
Author(s) -
Naomi Ikemoto,
H.S. Kim,
Makiko Kanazaki,
Yoshihito Ueno,
Satoshi Shuto,
Akira Matsuda,
Y. Wataya
Publication year - 1999
Publication title -
nucleic acids symposium series
Language(s) - English
Resource type - Journals
eISSN - 1746-8272
pISSN - 0261-3166
DOI - 10.1093/nass/42.1.89
Subject(s) - nuclease , succinate dehydrogenase , chemistry , protein subunit , pharmacology , antisense therapy , biology , biochemistry , microbiology and biotechnology , mitochondrion , oligonucleotide , enzyme , gene , locked nucleic acid
We investigated about targeting for new antimalarial drugs using antisense (AS) oligodeoxynucleotides (ODNs). Synthetic nuclease-resistant ODNs (phosphorothioate (PS) ODNs and ODNs containing 4'alpha-C-(2-aminoethyl)thymidines (4'-amino ODNs)) which target mitochondrial succinate dehydrogenase (SDH) iron-sulfur subunit (IP), had antimalarial activity (EC50; about 1.0 microM). Furthermore we showed that intra-parasitic SDH IP mRNA levels, which were detected using quantitative RT-PCR assay, were decreased 13% of control after the 24 h expose to SDH IP AS. From the results, we conclude that SDH has potential as the target for novel antimalarials, and AS ODNs is effective for search and assessment of targets for new antimalarial drugs.
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