药物结合破坏了DNA中的性水结构,第一个水化
Ty Santiago1, Daniel Konstantinovsky1,2, Matthew Tremblay1,3
1Department of Chemistry, Yale University New Haven CT 06520 USA ethan.perets@utsouthwestern.edu elsa.yan@yale.edu.
Chemical science
|March 20, 2025
概括
状SFG光谱学揭示了网素药物结合如何将强结合的水从DNA小槽中取代. 这一发现促进了对DNA水合和针对DNA的药物开发的理解.
科学领域:
- 生物物理学的生物物理.
- 化学物理 化学物理
- 分子生物学分子生物学
背景情况:
- 了解DNA水合对于DNA生物学和药物开发至关重要.
- 在分子相互作用期间探测*in situ*DNA水合变化是具有挑战性的.
研究的目的:
- 在药物结合时研究DNA水化结构的变化,使用合选择性振动总频率生成光谱学 (chiral SFG).
- 阐明水在网素与DNA的特定结合中的作用.
主要方法:
- 结合了实验和计算方法,使用了性SFG光谱学.
- 分析光谱变化以检测水位移和区分结态.
主要成果:
- 奇拉尔SFG成功地检测到在网素结合时,DNA小沟中的水位移.
- 该技术区分了与气结合较弱和较强的水分子.
- 网素偏好取代与胺碳基组相关的强接水.
结论:
- 奇拉尔SFG提供了对药物相互作用期间的DNA水化动态的机制性见解.
- 水分子在调节药物与DNA结合的局部特异性方面发挥着重要作用.
- 这些发现有望推动DNA向药物开发.
相关概念视频
Single-Strand DNA Binding Proteins
13.9K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
13.9K
DNA Base Pairing
26.6K
Erwin Chargaff’s rules on DNA equivalence paved the way for the discovery of base pairing in DNA. Chargaff’s rules state that in a double-stranded DNA molecule,
26.6K
Drug-Receptor Bonds
2.6K
Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.
In...
In...
2.6K
Overview of DNA Repair
29.8K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
29.8K
DNA Helicases
21.0K
DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
21.0K
Nucleosome Remodeling
8.9K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
8.9K


