| Mechanism of RNA cleavage catalyzed by sequence specific polyamide nucleic acid-neamine conjugate. | |
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MedLine Citation:
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PMID: 17854270 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In earlier studies, we found that a conjugate of neamine-polyamide nucleic acid targeting transactivation response element of HIV-1 RNA genome (HIV-1 TAR) displayed anti-HIV-1 activity and sequence-specific cleavage of the target RNA in vitro. Here we show that both the position of conjugation of polyamide nucleic acid (PNA) on neamine and the length of the spacer are critical parameters for conferring cleavage activity to the conjugate. The conjugation of PNA via a spacer incorporating 11 atoms to the 5-position of ring I of the neamine core conferred sequence-specific RNA cleavage activity on the conjugate, while conjugation to the 4'-position of ring II abolished this activity. Similarly, 5-neamine PNA complementary to TAR sequence of HIV-1 genome (PNA(TAR)) conjugates having either a 23-atom spacer or a bulky dansyl group between PNA and the neamine core also resulted in complete loss of cleavage activity. Based on these observations, we propose a mechanism for the observed RNA cleavage catalyzed by the conjugate involving unprotonated and protonated amino groups at the 3-position of ring I and the 6'-position of ring II of the neamine core, respectively. |
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Authors:
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Binay Chaubey; Snehlata Tripathi; Jérome Désiré; Isabelle Baussanne; Jean-Luc Décout; Virendra N Pandey |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oligonucleotides Volume: 17 ISSN: 1545-4576 ISO Abbreviation: Oligonucleotides Publication Date: 2007 |
Date Detail:
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Created Date: 2007-09-14 Completed Date: 2007-11-26 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101188415 Medline TA: Oligonucleotides Country: United States |
Other Details:
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Languages: eng Pagination: 302-13 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aminoglycosides
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chemistry,
metabolism* Cell Line Framycetin / chemistry, metabolism* HIV Long Terminal Repeat / genetics* HIV-1 / genetics*, metabolism Humans Hydrogen-Ion Concentration Nylons / metabolism Oligonucleotides, Antisense / chemistry*, metabolism* RNA, Viral / metabolism* Response Elements / genetics |
| Grant Support | |
ID/Acronym/Agency:
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AI142520/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Aminoglycosides; 0/Nylons; 0/Oligonucleotides, Antisense; 0/RNA, Viral; 119-04-0/Framycetin; 3947-65-7/neamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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