Orphan Ligand Receptor Deorphanization

Retrogenix Receptor Identification aids in the study of normal biological processes – or in understanding the mechanism of disease – has traditionally been hampered by the immense challenge in identifying the specific binding partners for a natural ligand or pathogen. Often these ‘orphan ligands’ bind to receptors or other types of proteins on the surface of human cells. Months or even years of research can be lost using standard protein chips or proteomics/mass spec-based approaches to attempt to identify these interactions. Low success rates coupled with the potential for false positives can slow things even further.

Off-Target Profiling Cell Microarray Technology
Discover high quality, exploitable drug targets and mechanisms of action as well as screening for potential off-targets.

Target Deconvolution Target Deconvolution
Accelerate phenotypic drug discovery through target deconvolution of phenotypic molecules.

Off-Target Screening Off-Target Screening
Understand cross-reactivity to reduce toxicity-based attrition and aid lead selection.

CAR Cell Specificity Screening CAR Cell Specificity Screening
Safely utilize a patient’s own immune system by precisely recognizing specific tumors.

Retrogenix Cell Microarray Technology is optimized for identifying physiologically-relevant cell surface interactions, vastly increasing the chances of receptor identification. This is facilitating breakthroughs in medical research, including the identification of a key receptor involved in severe childhood malaria which was reported in the journal, Nature1.

Let us confirm and validate stages to determine if any receptor ‘hit’ is reproducible and specific to the test ligand in a range of conditions. We also provide identification that is dependent on post-translational modifications to the target (such as glycosylation or folding).

Versatile Across a Range of Ligands

We have the ability to conduct receptor identification of a wide range of molecules ranging from purified proteins to more complex ligands such as whole cells. We have the capability to uncover specific human receptors for:

  • Natural soluble proteins and peptides
  • Live viruses and virus-like particles (VLPs)
  • Cell surface-derived ligands (i.e. those mediating cell:cell interactions)
  • Whole cells expressing the ligand of interest
  • Parasite-infected red blood cells
  • Plasma samples from patients

Optimize Your Program

Sensitive and Specific

The highly-sensitive technology is capable of detecting micromolar affinity ligand-receptor interactions even in the absence of any amplification strategies. Our receptor identification process includes a final confirmation screen which is undertaken to determine that the receptor ‘hit’ is reproducible and specific to the test ligand. Binding that is dependent on post-translational modifications to the target (such as glycosylation or folding) can also be detected – a real advantage over traditional protein microarrays.

Rapid determination of specific ligand-receptor interactions can be extremely cost-effective. An analysis by one of our pharmaceutical clients estimated that in-house methods required around 10x the investment of our screen to produce the same number of successful results. Achieving more meaningful results quicker can maintain a project’s momentum and can provide a competitive edge in being first to publish. Open the door to new opportunities for therapeutic development with increased patient advantage and commercial benefit.

 

References:

Turner L et al. Severe malaria is associated with parasite binding to endothelial protein C receptor Nature 2013, 498:502.

 

Frequently Asked Questions (FAQs) for Receptor Identification