HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Compagno, D. Articles by Toulmé, J.-J. Search for Related Content PubMed PubMed Citation Articles by Compagno, D. Articles by Toulmé, J.-J. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 12, 8191-8198, March 19, 1999

Antisense Oligonucleotides Containing Modified Bases Inhibit in Vitro Translation of Leishmania amazonensis mRNAs by Invading the Mini-exon Hairpin

Daniel Compagno, Jed N. Lampe^§, Chantal Bourget, Igor V. Kutyavin^§, Ludmila Yurchenko^¶, Eugeny A. Lukhtanov^§, Vladimir V. Gorn^§, Howard B. Gamper Jr.^§, and Jean-Jacques Toulmé

From  INSERM Unité 386, IFR Pathologies Infectieuses, Université Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux, France, ^§ Epoch Pharmaceuticals, Inc., Bothell, Washington 98021, and the ^¶ Institute of Biorganic Chemistry, Lavrentiev Prospekt 8, Novosibirsk, Russia

Complementary oligodeoxynucleotides (ODNs) that contain 2-aminoadenine and 2-thiothymine interact weakly with each other but form stable hybrids with unmodified complements. These selectively binding complementary (SBC) agents can invade duplex DNA and hybridize to each strand (Kutyavin, I. V., Rhinehart, R. L., Lukhtanov, E. A., Gorn, V. V., Meyer, R. B., and Gamper, H. B. (1996) Biochemistry 35, 11170-11176). Antisense ODNs with similar properties should be less encumbered by RNA secondary structure. Here we show that SBC ODNs strand invade a hairpin in the mini-exon RNA of Leishmania amazonensis and that the resulting heteroduplexes are substrates for Escherichia coli RNase H. SBC ODNs either with phosphodiester or phosphorothioate backbones form more stable hybrids with RNA than normal base (NB) ODNs. Optimal binding was observed when the entire hairpin sequence was targeted. Translation of L. amazonensis mRNA in a cell-free extract was more efficiently inhibited by SBC ODNs complementary to the mini-exon hairpin than by the corresponding NB ODNs. Nonspecific protein binding in the cell-free extract by phosphorothioate SBC ODNs rendered them ineffective as antisense agents in vitro. SBC phosphorothioate ODNs displayed a modest but significant improvement of leishmanicidal properties compared with NB phosphorothioate ODNs.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati