LifeTein’s Innovative Synthetic Wasabi Receptor Toxin Peptides and Its Variants Propel Breakthrough in Chronic Pain Research

LifeTein’s groundbreaking work in synthetic peptides, including the Wasabi Receptor Toxin, its mutants, Biotinylated, and AlexaFluor-488 conjugated variants, has played a pivotal role in advancing our understanding of chronic pain mechanisms. This research supported the efforts of David Julius, who was awarded the Nobel Prize in Physiology or Medicine this year for his contributions.

Julius, along with his team at the University of California, San Francisco (UCSF), made a significant discovery involving a scorpion toxin that specifically targets the “wasabi receptor.” This receptor is an ion channel protein that triggers the intense sensations, such as the sinus-clearing effect of wasabi or the eye-watering pain from cutting onions.

The team’s research highlighted that the scorpion toxin, referred to as WaTx, activates the TRPA1 wasabi receptor, inducing a pain response to various irritants. Remarkably, WaTx is a novel type of cell-penetrating peptide that can enter cells directly across the plasma membrane without the need for channel proteins.

The implications of this discovery are vast, with potential applications in studying and treating chronic pain and inflammation. The unique properties of WaTx suggest it could be instrumental in developing new, non-opioid pain management therapies, as it induces pain and hypersensitivity without causing neurogenic inflammation.

David Julius’s research, particularly his exploration of receptors that detect temperature, has been recognized with the prestigious Nobel Prize in Physiology or Medicine 2021, underscoring the impact of his work on the medical and scientific community.

This research was documented in a study published by Lin King, J. V., Emrick, J. J., Kelly, M. J. S., Herzig, V., King, G. F., Medzihradszky, K. F., & Julius, D. (2019) in the journal Cell, where they discuss the mode-specific modulation of TRPA1 and its implications for pain management.

Histone H3K27M is a driving mutation in diffuse intrinsic pontine glioma (DIPG), a deadly pediatric brain tumor. The malignant and treatment-resistant brain tumor is a target for anti-cancer studies using cell penetrating peptides.

Through a global inhibition of PRC2 catalytic activity and displacement of H3K27me2/3, H3K27M reshapes the epigenome and promotes oncogenesis of DIPG. Consequentially, the histone modification H3K36me2, antagonistic to H3K27me2/3, is elevated. The relationship and role of H3K36me2 in H3K27M-DIPG was investigated by approaches to its upstream catalyzing enzymes, NSD1 and NSD2, the “writers”, and its downstream binding factors, LEDGF and HDGF2, the “readers”.

Tumor-promoting transcriptional programs in H3K27M-DIPG were found to be disrupted by loss of NSD1 and NSD2, thus impeding cellular proliferation and tumorigenesis.
Downstream, a chemically modified peptide mimicking endogenous H3K36me2 was found to dislodge LEDGF and HDGF2 from chromatin. As LEDGF and HDGF2 are the main readers mediating the protumorigenic effects downstream of NSD1/2-H3K36me2, dislodging them resulted in inhibition of H3K27M-DIPG proliferation.

In this study, the chemically modified peptides used were cell penetrating peptides purchased from LifeTein.

Reference: Sci. Adv. 2021 Jul 14; 7(29)