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2つの2'-O-改変核酸アナログの間の化学の小さな違いにもかかわらず,RNA親和性の大きな違いの構造的合理化
Rekha Pattanayek1, Latsavongsakda Sethaphong, Chongle Pan
1Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232, USA.
Journal of the American Chemical Society
|November 19, 2004
まとめ
アンチセンセオリゴヌクレオチド (AON) の化学的変異は,そのRNA結合に影響する. 2'-O-NMAの改変はRNAの親和性を高め,2'-O-NMCは構造的および水分化の違いのためにそれを減少させる.
科学分野:
- 薬用化学 薬用化学について
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- リボースの2位における化学的変化により,性能が向上した反意味オリゴヌクレオチド (AON) が生成されます.
- 2 -O-[2-(メトキシ) エチル] (MOE) のような置換物は,RNAの親和性と細胞の吸収を高めます.
- 2 - 置換はヌクレアース抵抗性を高め,リポフィリティを変化させる可能性があります.
研究 の 目的:
- 2 -O-[2-(メチラミノ) -2-オクソエチル] (NMA) と2 -O-(N-メチルカルバマート) (NMC) の改変が,AON RNAの親和性に与える異なった影響を調査する.
- NMAとNMCで改変されたAONの間の熱力学的安定性における観察された差異の構造的根拠を解明する.
主な方法:
- 2 -O-NMA-Tまたは2 -O-NMC-Tを含むA型DNA二重複体の高解像度結晶構造の決定.
- 複合体内の置換体構成と水分子相互作用の分析.
主要な成果:
- 2 -O-NMA-Tの組み込みはRNAの親和性を著しく改善する.
- 2 -O-NMC-Tの組み込みはRNAの親和性を劇的に低下させます.
- NMAの置換物は,水分子を捕まえて,MOEの改変を模倣して,拡張された形状を採用します.
- NMCの置換剤は不利な静電相互作用を示し,安定した水構造がなく,熱力学的安定性が低下します.
結論:
- 2 - 置換物の構成性および水分化特性は,AONの安定性とRNAの親和性に重大な影響を及ぼします.
- NMAの修正は,有利な構造と水分効果を通じてAONのパフォーマンスを向上させます.
- NMCの改変は,不利な相互作用と水分化パターンの障害により,AONを不安定化させます.
関連する概念動画
01:23RNA Structure
Overview
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
01:53RNA Stability
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
01:23RNA Structure
Overview
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
01:53RNA Stability
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
01:19RNA Structure
The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
01:25Nucleic Acid Structure
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA has a double-helix structure. The...
DNA Structure
DNA has a double-helix structure. The...