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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-7-29
pubmed:abstractText
Deoxyribonucleic acid (DNA) gyrase is an important enzyme that facilitates the movement of replication and transcription complexes through DNA by creating negative supercoils ahead of the complex. Its presence in Plasmodium falciparum is now established and considered a good drug target since it is absent in the human host. The sequence of P. falciparum gyrase A subunit was analyzed for its messenger ribonucleic acid (mRNA) folding as well as target accessibility for ribozymes. The four GUC triplet sites identified at 334, 491, 1907, and 2642 nucleotide positions of the Gyrase A mRNA were also accessible to oligos by RNase H assay. Site GUC491 was optimally accessible followed by GUC1907, GUC334, and GUC2642 sites. Ribozymes were produced against all these sites and tested for their in vitro transcript cleavage potentials where RZ491 showed the maximum cleavage rate. Therefore, this ribozyme (RZ491) was chemically synthesized albeit with modifications so as to make it resistant against ribonuclease attack. The modified ribozyme retained its cleavage potential and was able to inhibit the P. falciparum parasite growth up to 49.54% and 74.77% at 20 and 30 microM ribozyme concentrations, respectively, as compared to the untreated culture. However, up to 20% and 24.32% parasite growth inhibition was observed at the same ribozyme concentrations of 20 and 30 microM when compared with control ribozyme-treated cultures. This ribozyme as well as other targets identified here can be investigated further to develop the effective chemotherapeutic agents against malaria.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0932-0113
pubmed:author
pubmed:issnType
Print
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
751-63
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Ribozyme cleavage of Plasmodium falciparum gyrase A gene transcript affects the parasite growth.
pubmed:affiliation
Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't