High-affinity RNA ligands to human α-thrombin
Systematic Evolution of Ligands by Exponential enrichment (SELEX) was used to isolate from a population of 1013 RNA molecules two classes of high affinity RNAs that bind specifically to human α-thrombin. Class I RNAs are represented by a 24-nucleotide RNA (RNA 16.24), and class II RNAs are represent...
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Published in | Nucleic acids research Vol. 22; no. 13; pp. 2619 - 2626 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Oxford University Press
11.07.1994
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Subjects | |
Online Access | Get full text |
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Summary: | Systematic Evolution of Ligands by Exponential enrichment (SELEX) was used to isolate from a population of 1013 RNA molecules two classes of high affinity RNAs that bind specifically to human α-thrombin. Class I RNAs are represented by a 24-nucleotide RNA (RNA 16.24), and class II RNAs are represented by a 33-nucleotide RNA (RNA 27.33). RNA 16.24 inhibits thrombin-catalyzed fibrin clot formation in vitro. Secondary structures are proposed for these RNAs, revealing a novel stem-loop structure for RNA 16.24, comprised of an unusually large 16-nucleotide loop. Mutants of RNA 16.24 were generated to investigate structural features critical to high-affinity binding. Phosphate modification with ethylnitrosourea identified regions of the RNAs necessary for electrostatic interactions. Competition with heparin suggests that these RNAs bind the electropositive heparinbinding site of thrombin. These ligands represent a novel class of thrombin inhibitors that may be suitable for therapeutic or diagnostic applications. |
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Bibliography: | istex:DDCB5E7F761CE3A65848A34B70DCB8204A036F8E ArticleID:22.13.2619 ark:/67375/HXZ-11X6SB1T-6 To whom correspondence should be addressed ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0305-1048 1362-4962 |
DOI: | 10.1093/nar/22.13.2619 |