Implication of RNA structure on antisense oligonucleotide hybridization kinetics
A 47-nucleotide transcript of the activated Ha-ras gene was prepared and determined, by enzymatic structure mapping, to form a stable hairpin structure. Six antisense decaribonucleotides were designed, and association constants (Ka) for the hairpin- and length-matched complements were measured. Two of the antisense oligonucleotides targeted to the loop had nearly equal affinity for the transcript compared to the complement. The others, including one oligonucleotide complementary to the 3' side of the single-stranded loop, bound 10(5)-10(6)-fold less tightly to the transcript than to the short complement. We propose the difference in affinity is due to the target structure, both the secondary structure of the stem and the structure in the loop. Measurement of the bimolecular association rate constant, k1, and the dissociation rate constant, k-1, for these oligonucleotides indicates the observed relationship between affinity and structure is primarily due to k1.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1992 |
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| Erschienen: |
1992 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
Biochemistry - 31(1992), 48 vom: 08. Dez., Seite 12055-61 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lima, W F [VerfasserIn] |
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| Themen: |
63231-63-0 |
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| Anmerkungen: |
Date Completed 08.01.1993 Date Revised 13.06.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM012612243 |
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| 100 | 1 | |a Lima, W F |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Implication of RNA structure on antisense oligonucleotide hybridization kinetics |
| 264 | 1 | |c 1992 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
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| 500 | |a Date Completed 08.01.1993 | ||
| 500 | |a Date Revised 13.06.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a A 47-nucleotide transcript of the activated Ha-ras gene was prepared and determined, by enzymatic structure mapping, to form a stable hairpin structure. Six antisense decaribonucleotides were designed, and association constants (Ka) for the hairpin- and length-matched complements were measured. Two of the antisense oligonucleotides targeted to the loop had nearly equal affinity for the transcript compared to the complement. The others, including one oligonucleotide complementary to the 3' side of the single-stranded loop, bound 10(5)-10(6)-fold less tightly to the transcript than to the short complement. We propose the difference in affinity is due to the target structure, both the secondary structure of the stem and the structure in the loop. Measurement of the bimolecular association rate constant, k1, and the dissociation rate constant, k-1, for these oligonucleotides indicates the observed relationship between affinity and structure is primarily due to k1 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Oligonucleotides, Antisense |2 NLM | |
| 650 | 7 | |a RNA |2 NLM | |
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| 650 | 7 | |a Proto-Oncogene Proteins p21(ras) |2 NLM | |
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| 700 | 1 | |a Ecker, D J |e verfasserin |4 aut | |
| 700 | 1 | |a Freier, S M |e verfasserin |4 aut | |
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