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相关概念视频

DNA Replication02:40

DNA Replication

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DNA replication involves the separation of the two strands of the double helix, with each strand serving as a template from which the new complementary strand is copied.  After replication, each double-stranded DNA includes one parental or “old” strand and one “new” strand. This is known as semiconservative replication. The resulting DNA molecules have the same sequence and are divided equally into the two daughter cells.
Replication in Prokaryotes
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Lagging Strand Synthesis01:59

Lagging Strand Synthesis

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During replication, the complementary strands in double-stranded DNA are synthesized at different rates. Replication first begins on the leading strand. Replication starts later, occurs more slowly, and proceeds discontinuously on the lagging strand.
There are several major differences between synthesis of the leading strand and synthesis of the lagging strand. 1) Leading strand synthesis happens in the direction of replication fork opening, whereas lagging strand synthesis happens in the...
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Maxam-Gilbert Sequencing01:05

Maxam-Gilbert Sequencing

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In the same year as the discovery of the Sanger sequencing method, another group of scientists, Allan Maxam and Walter Gilbert, demonstrated their chemical-cleavage method for DNA sequencing. The Maxam-Gilbert method relies on using different chemicals that can cleave the DNA sequence at specific sites, the separation of resulting DNA fragments of variable size using electrophoresis, and deciphering the DNA sequence from the resulting gel bands.
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The Replisome03:01

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DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
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Translesion DNA Polymerases02:10

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Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
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The DNA Replication Fork01:02

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An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork.   Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
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High-Density DNA and RNA microarrays - Photolithographic Synthesis, Hybridization and Preparation of Large Nucleic Acid Libraries
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对于DNA编码图书馆合成的squaramide形成

Antoine Douchez1, Julien Poupart1, Gaoqiang Yang1

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概括

用DNA编码的图书馆 (DEL) 允许发现小分子. 一种新的,温和的squaramide反应是DNA安全的,并且与DELs兼容,扩大了药物发现的可访问化学支架.

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科学领域:

  • 药用化学 医学化学
  • 化学生物学 化学生物学
  • 有机合成 有机合成

背景情况:

  • DNA编码库 (DEL) 是发现生物活性的小分子的强大工具.
  • 在DEL的关键挑战包括开发水相反应,最大限度地减少DNA损伤,并纳入各种化学构件.
  • 在DEL中获得药物化学的新型支架通常受到DNA支持的化学约束的限制.

研究的目的:

  • 开发一种新的,与DNA兼容的化学转换,用于DNA编码图书馆合成.
  • 建立一个强大的方胺形成反应,适合在DNA化学.
  • 扩大使用DEL技术用于药物发现的可访问化学支架的范围.

主要方法:

  • 设计和优化了一种两步方胺形成反应.
  • 评估了反应与水条件的兼容性和DNA完整性.
  • 评估了反应对各种功能组的耐受性及其产量.

主要成果:

  • 成功开发了一种温和高产的两步方胺形成反应.
  • 该反应对广泛的功能群体表现出极好的耐受性.
  • 该方法被证明对DNA是安全的,导致最小的改变.
  • 该反应适合集成到DNA编码库工作流程中.

结论:

  • 开发的正方体形成反应是DNA编码库的理想方法.
  • 这种进步扩大了通过DELs可访问的化学支架的范围.
  • 这种反应有助于发现具有潜在生物应用的新型小分子.