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Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
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Programing Chemical Communication: Allostery vs Multivalent Mechanism.

Dominic Lauzon1, Alexis Vallée-Bélisle1

  • 1Département de Chimie, Laboratoire de Biosenseurs et Nanomachines, Université de Montréal, Montréal QC H2V 0B3, Canada.

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|August 15, 2023
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Summary
This summary is machine-generated.

Researchers engineered a DNA-based molecular switch controllable by multivalent or allosteric activators. Multivalent activation offers greater versatility in tuning switch properties, promising applications in biosensing and synthetic biology.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Synthetic Biology

Background:

  • Life's emergence depends on chemical communication and integrating inputs into outputs.
  • Nature utilizes allostery and multivalent activation for signal integration.
  • Allostery is well-understood for molecular switch optimization, but multivalent activation is less understood.

Purpose of the Study:

  • To compare the thermodynamic basis and design principles of allosteric and multivalent activation.
  • To engineer a programmable DNA-based molecular switch.
  • To investigate the tunability of molecular switches using different activation mechanisms.

Main Methods:

  • Engineered a DNA-based molecular switch.
  • Designed DNA activators for both multivalent and allosteric mechanisms.
  • Analyzed binding affinity, dynamic range, and activated half-life.

Main Results:

  • Demonstrated a programmable DNA-based switch triggered by multivalent or allosteric DNA activators.
  • Showcased that multivalent activation allows for more versatile programming of switch affinity, dynamic range, and half-life compared to allosteric activation.
  • Precisely designed binding interfaces for multivalent activators.

Conclusions:

  • Multivalent assembly offers a simple and rational approach to tune molecular switch properties.
  • This mechanism provides greater versatility than allosteric activation for controlling molecular switches.
  • Potential applications include biosensing, drug delivery, synthetic biology, and molecular computation.