Incorporation of 5-(N-aminohexyl)carbamoyl-2'-O-methyluridine ((N)Um) into oligonucleotides increases antisense properties such as RNA binding affinity, nuclease resistance and RNase H activity. The present X-ray studies on hybrid duplexes formed between antisense oligonucleotides containing (N)Um and their target RNAs have revealed the structural basis for such properties. The terminal ammonium groups of the aminohexyl chains interact with the phosphate oxygen anions. The 2'-O-methyl modification induces the ribose group to adopt the C3'-endo conformation. Comparisons with the structure of unmodified duplex show that the (N)Um incorporation narrows the minor grooves and alters their hydration structures. These structural changes are well correlated to the favorable properties for useful antisense molecules.

Download full-text PDF

Source
http://dx.doi.org/10.1093/nass/49.1.65DOI Listing

Publication Analysis

Top Keywords

hybrid duplexes
8
antisense oligonucleotides
8
target rnas
8
x-ray analyses
4
analyses hybrid
4
antisense
4
duplexes antisense
4
oligonucleotides 5-n-aminohexylcarbamoyl-2'-o-methyluridine
4
5-n-aminohexylcarbamoyl-2'-o-methyluridine target
4
rnas incorporation
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!