Abstract:
:Binding enhancement by tertiary interactions is a strategy that takes advantage of the higher order folding of functionally important RNAs to bind short nucleic acid-based compounds tightly and more specifically than possible by simple base pairing. For example, tertiary interactions enhance binding of specific hexamers to a group I intron ribozyme from the opportunistic pathogen Pneumocystis carinii by 1,000- to 100,000-fold relative to binding by only base pairing. One such hexamer, d(AnTnGnAnCn)rU, contains an N3' --> P5' phosphoramidate deoxysugar-phosphate backbone (n) that is resistant to chemical and enzymatic decay. Here, it is shown that this hexamer is also a suicide inhibitor of the intron's self-splicing reaction in vitro. The hexamer is ligated in trans to the 3' exon of the precursor, producing dead-end products. At 4 mM Mg2+, the fraction of trans-spliced product is greater than normally spliced product at hexamer concentrations as low as 200 nM. This provides an additional level of specificity for compounds that can exploit the catalytic potential of complexes with RNA targets.
journal_name
Proc Natl Acad Sci U S Aauthors
Testa SM,Gryaznov SM,Turner DHdoi
10.1073/pnas.96.6.2734keywords:
subject
Has Abstractpub_date
1999-03-16 00:00:00pages
2734-9issue
6eissn
0027-8424issn
1091-6490journal_volume
96pub_type
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