Intracellular Delivery of Small Molecule Reactive Ligands for Bioconjugation

A protected small molecule probe is delivered intracellularly and subsequently releases an aryl diazonium ion for use as a bioconjugation agent or drug delivery agent.  This technology enables a novel chemical probe for observing intact biological…

A protected small molecule probe is delivered intracellularly and subsequently releases an aryl diazonium ion for use as a bioconjugation agent or drug delivery agent. This technology enables a novel chemical probe for observing intact biological cells.

Background:
Selectivity in biological systems comes from a complex interplay of location, interactions, and reactivity. Covalent small-molecule probes offer great potential in the development of chemical tools to study intracellular proteins. A challenge within this area is in garnering selectivity associated with location. For example, in order to gain accessibility to intracellular proteins, small-molecule labeling strategies have relied on working with cell lysate, yet key contextual interactions associated with localization within the cell are lost during lysis.

Aryl diazonium ions are known for their selective reactivity with the electron-rich aromatic tyrosine side chain. But aryl diazonium ions for use as probes have suffered from a lack of deliverability since they have short half-lives and are generally unstable.

The present invention provides probes, e.g., protected triazabutadiene probes, that selectively release benzene diazonium ions (BDIs) intracellularly, providing a tool for cellular studies in intact biological systems, e.g., a means for accessing and/or labeling intracellular proteins or molecules prior to cell lysis.

Applications:

  • Protein labeling
  • Bioconjugation
  • Drug discovery
  • Life science research
  • Tyrosine studies
  • Histidine studies

Advantages:

  • Enables in cellular studies
  • Covalent binding
  • Tunable chemistry for selectivity and delivery

Website

https://arizona.technologypublisher.com/tech/Intracellular_Delivery_of_Small_Molecule_Reactive_Ligands_for_Bioconjugation