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Related Concept Videos

Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
Lagging Strand Synthesis01:59

Lagging Strand Synthesis

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...
Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
Maxam-Gilbert Sequencing01:05

Maxam-Gilbert Sequencing

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.
Challenges of the Maxam-Gilbert Method
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Next-generation Sequencing03:00

Next-generation Sequencing

The first human genome sequencing project cost $2.7 billion and was declared complete in 2003, after 15 years of international cooperation and collaboration between several research teams and funding agencies. Today, with the advent of next-generation sequencing technologies, the cost and time of sequencing a human genome have dropped over 100 fold.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features.

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Related Experiment Video

Updated: Jun 2, 2026

Construction of Synthetic Phage Displayed Fab Library with Tailored Diversity
12:31

Construction of Synthetic Phage Displayed Fab Library with Tailored Diversity

Published on: May 1, 2018

Route to three-dimensional fragments using diversity-oriented synthesis.

Alvin W Hung1, Alex Ramek, Yikai Wang

  • 1Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA.

Proceedings of the National Academy of Sciences of the United States of America
|April 13, 2011
PubMed
Summary
This summary is machine-generated.

Fragment-based drug discovery (FBDD) benefits from diverse chemical libraries. This study applies diversity-oriented synthesis (DOS) to create novel, 3D-rich fragments, expanding chemical space for drug discovery screening.

More Related Videos

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source
08:35

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source

Published on: May 29, 2021

Related Experiment Videos

Last Updated: Jun 2, 2026

Construction of Synthetic Phage Displayed Fab Library with Tailored Diversity
12:31

Construction of Synthetic Phage Displayed Fab Library with Tailored Diversity

Published on: May 1, 2018

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source
08:35

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source

Published on: May 29, 2021

Area of Science:

  • Medicinal Chemistry
  • Drug Discovery
  • Chemical Synthesis

Background:

  • Fragment-based drug discovery (FBDD) is effective for generating drug leads.
  • Current FBDD relies heavily on sp(2)-rich aromatic fragments.
  • Expanding fragment libraries to include 3D structures can enhance chemical space exploration.

Purpose of the Study:

  • To apply diversity-oriented synthesis (DOS) for creating novel fragment libraries.
  • To generate fragments with highly sp(3)-rich skeletons for FBDD screening.
  • To characterize the properties of these new 3D fragments.

Main Methods:

  • Utilized diversity-oriented synthesis (DOS) to construct unique molecular skeletons.
  • Synthesized a novel set of fragments with high sp(3)-hybridization character.
  • Employed cheminformatic analysis to quantify fragment properties (shape, physical characteristics).

Main Results:

  • Successfully generated a library of novel 3D fragments.
  • The new fragments possess highly sp(3)-rich skeletons, differing from typical FBDD libraries.
  • Cheminformatic analysis confirmed the distinct shapes and properties of the 3D fragments compared to existing fragment databases.

Conclusions:

  • Diversity-oriented synthesis is a viable strategy for creating novel, 3D-rich fragment libraries.
  • These expanded fragment sets offer access to unexplored chemical space for FBDD.
  • The characterized 3D fragments can serve as valuable starting points for drug discovery targeting challenging biological targets.