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Automated Delivery of Microfabricated Targets for Intense Laser Irradiation Experiments
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Kinetic target-guided synthesis.

Xiangdong Hu1, Roman Manetsch

  • 1Department of Chemistry, University of South Florida, 4202 E. Fowler Avenue, CHE205 A, Tampa, FL 33620, USA.

Chemical Society Reviews
|March 24, 2010
PubMed
Summary

Target-guided synthesis (TGS) streamlines drug discovery by having proteins assemble their own ligands. This review explores kinetic TGS methods beyond click chemistry for potent inhibitor development.

Area of Science:

  • Medicinal Chemistry
  • Chemical Biology
  • Drug Discovery

Background:

  • Target-guided synthesis (TGS) integrates fragment screening and synthesis for efficient drug discovery.
  • Kinetic TGS utilizes irreversible reactions to assemble inhibitors in the presence of a target protein.
  • Existing kinetic TGS methods, particularly in situ click chemistry, have identified potent inhibitors.

Purpose of the Study:

  • To review kinetic target-guided synthesis (TGS) approaches excluding 1,3-dipolar cycloaddition.
  • To detail the features and advantages of these specific kinetic TGS strategies.
  • To highlight the potential of these methods in accelerating drug discovery.

Main Methods:

  • Focus on kinetic TGS approaches that employ irreversible reactions.

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  • Analysis of strategies combining reactive fragments facilitated by target protein binding.
  • Exclusion of 1,3-dipolar cycloaddition reactions (click chemistry) from the main discussion.

    • Main Results:

    • Kinetic TGS, leveraging slow reactions and high-affinity fragments, enables efficient inhibitor assembly.
    • These methods offer a streamlined approach to drug discovery by combining screening and synthesis.
    • Successful identification of potent inhibitors has been demonstrated through kinetic TGS.

    Conclusions:

    • Kinetic TGS approaches, beyond click chemistry, present a promising avenue for drug discovery.
    • The described methods offer unique advantages for developing targeted inhibitors.
    • Further exploration of these TGS strategies can significantly accelerate the identification of novel therapeutics.