Antimicrobial Peptides Isolated from Feline Skin Inhibit Drug-Resistant S. Pseudintermedius Pathogen

Author’s cat, Nappa. Not a feline from the experiment.

Methicillin-resistant Staphylococcus pseudintermedius (MRSP), a zoonotic pathogen causing severe skin infection, has been shown to be combated by peptides with antimicrobial and anti-inflammatory properties. The phenol-soluble modulin beta (PSMβ) peptides that succeed where conventional drugs fall short are isolated from a unique strain (S. felis C4) found in feline skin.

Antimicrobial Peptides from Feline Skin

Once the PSMβ peptides were identified from the S. felis strain, LifeTein helped the scientists by synthesizing batches of the peptides to be tested against MRSP in mice. Results showed significant reduction in necrotic skin injury from MRSP in mice treated with the S. felis extract. This was due to the antimicrobial peptides inhibiting translation and disrupting bacterial cell membranes, greatly reducing skin colonization of MRSP.

The group believes this study can re-establish the community of microbes on skin that promote health. The results proved effective in vitro and in vivo when combatting MRSP. Overall, the discovery serves to represent a potential bacteriotherapeutic for both human and animal skin diseases like the MRSP colonization and infection.

O’Neill AM, Worthing KA, Kulkarni N, et al. Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant S. pseudintermedius. Elife. 2021;10:e66793. Published 2021 Oct 19. doi:10.7554/eLife.66793

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Valporate Peptides and Respiratory Treatment

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Valporate Peptides by LifeTein Pave Way for Future of Respiratory Distress Treatment

Nephrilin peptides have proven to have several beneficial systemic effects in rodent models of stress, burn, and sepsis by reducing present pro-inflammatory factors. Scientists in Sunnyvale, CA were keen on testing these nephrilin-class peptides on models of respiratory distress, applying their beneficial properties to rat scald-endotoxemia models. LifeTein synthesized specially designed peptides with Valproic acid covalently attached to the N-terminus to be tested on the scald-endotoxemia models.

Valporic Acid Enhances Nephrilin Peptides

Three peptides in total were synthesized for the group by LifeTein, Nmod3sN1v, Nmod3N1vA, and Nmod3N1vAS3, whose sequences can be seen in the figure. The latter two peptides differ from Nmod3sN1v in that they contain the tripeptide sequence d(AVD), since the tripeptide has shown to dramatically improve iron-binding in vitro. Nmod3N1vAS3 differs from Nmod3N1vA in that it contains a Y*LK motif (where Y* is phosphotyrosine). This motif was previously shown to inhibit STAT3 activation, a suspected role in lung inflammation pathology.

After treating the rat scald-endotoxemia models with the peptides, the group concluded that the Nmod3N1vA and Nmod3N1vAS3 peptides were superior than the Nmod3sN1v sequence in the following readings: protease-stability, biodistribution to lung tissue, amelioration of catabolism, early inflammation and insulin-resistance, activated lymph node dendritic / T-cells, breathing difficulty (by oximetry), lung edema, granulocyte count and IL1-beta in BAL fluid, systemic oxidative stress and kidney function. The group concluded that when compared to the original nephrilin peptide, these designs are at least ten times more potent by weight. The study showcases the potential these peptide designs hold for future drug development, especially in respiratory models and burn damage.

References: Desmond D. Mascarenhas, Puja Ravikumar, Edward P. Amento, N-modulin peptides attenuate respiratory distress in a scald-endotoxemia model, Burns Open, Volume 6, Issue 1, 2022, Pages 1-6, ISSN 2468-9122, https://doi.org/10.1016/j.burnso.2021.09.001.

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LifeTein’s Peptides and Antibodies Help Scientists Fight Dementia-causing Pathogens in Zebrafish Model

Neurodegeneration in postmortem patients of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) has been correlated to distribution of dipeptide repeat proteins in the form of poly-GR. Scientists at the Erasmus University Medical Center Rotterdam have assessed the toxicity of poly-GR and found a possible suppression with the help of zebrafish, Trolox, and LifeTein’s own GR peptides and antibodies.

Trolox Suppresses Poly-GR Toxicity Identified by Antibodies

Using zebrafish as a model for C9FTD/ALS cases, scientists injected the embryos with RNA encoding ATG mediated codon-optimized 100xGR. These peptides provided by LifeTein were able to simulate the apoptosis in the brain and caused aberrant motor neuron morphology in the zebrafish embryos. Using LifeTein’s monoclonal antibody against poly-GR, the group was able to detect the poly-GR specifically in the brain.

The researchers’ study suggested inhibition of oxidative stress held the potential to suppress the poly-GR toxicity in these models. To apply this knowledge, the embryos were treated with Trolox, a known inhibitor of oxidative stress. Not only did this rescue the poly-GR toxicity, but it did so in vivo. This holds a promising future in treatment of C9FTD/ALS patients, indicating the possible role of oxidative stress implies the possible treatment by inhibiting the said stress.

References: Riemslagh FW, Verhagen RFM, van der Toorn EC, Smits DJ, Quint WH, van der Linde HC, van Ham TJ, Willemsen R. Reduction of oxidative stress suppresses poly-GR mediated toxicity in zebrafish embryos. Dis Model Mech. 2021 Oct 25:dmm.049092. doi: 10.1242/dmm.049092. Epub ahead of print. PMID: 34693978.

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Lifetein’s Photocleavable Linkers Assist Advancement of Microrobots in Anticancer Drug Delivery

The use of mobile microrobots offers a promising solution for targeted medical theranostic applications at normally inaccessible regions of the human body. Namely, the circulatory system is an ideal region for said applications, but blood flow can complicate both navigation inside the body and preservation of the microrobots.

Researchers have designed microrollers able to be controlled via magnetic propulsion and steering, able to maneuver against physiologically relevant blood flow effectively. The rollers are composed of a magnetically responsive half-side and a silica half-side for cargo loading and biochemical functionalities. Once navigated to cancerous cell monolayers, the rollers utilize surface-functionalized cell-specific antibodies as well as photocleavable linkers to release doxorubicin (DOX), and anticancer drug molecule, onto the target area.

Both the azide-DOX and o-nitrobenzyl photocleavable linker used by the team were provided by LifeTein, allowing the mircorollers to release the drug on demand via UV light exposure. This method of on demand delivery of the drug molecules combined with maneuverability of the microrollers designed by the researchers opens the door for development of next-generation microrobots for controlled navigation and cargo delivery in the circulatory system.

Reference: Alapan et al., Sci. Robot. 5, eaba5726 (2020) 20 May 2020


LifeTein’s Synthetic Scorpion Toxin Peptides Helped Nobel Prize Winner and Team Unravel Chronic Pain Mechanisms

Scorpion Toxin Peptides By Nobel Prize Winner David Julius

LifeTein’s synthetic Wasabi Receptor Toxin, Wasabi Receptor Toxin Mutants, Biotinylated Wasabi Receptor Toxin, and AlexaFluor-488 conjugated Wasabi Receptor Toxin and Mutants helped scientists unravel chronic pain mechanisms. Among this team was David Julius, corecipient of this year’s Nobel Prize in Physiology or Medicine.

Julius and fellow researchers at the University of California, San Francisco (UCSF) have identified a scorpion toxin that targets the “wasabi receptor”. The wasabi receptor is an ion channel protein that is responsible for the sinus-clearing or eye-stinging pain experienced when eating wasabi or chopping onions.

It was found that the scorpion toxin, a peptide as the wasabi receptor toxin, or WaTx, activates the wasabi receptor TRPA1 and triggers this pain response to irritants. The WaTx peptide is a novel cell-penetrating peptide and can directly pass through the plasma membrane, without needing to traverse through channel proteins.

The WaTx peptide could be used to study chronic pain and inflammation and may lead to the development of novel non-opioid pain therapies. WaTx produces pain and pain hypersensitivity, but not neurogenic inflammation.

Congratulations to David Julius, whose in-depth research in receptors lead to the discovery of receptors for temperature was rewarded with The Nobel Prize in Physiology or Medicine 2021.

Reference: Lin King, J. V., Emrick, J. J., Kelly, M. J. S., Herzig, V., King, G. F., Medzihradszky, K. F., & Julius, D. (2019). A Cell-Penetrating Scorpion Toxin Enables Mode-Specific Modulation of TRPA1 and Pain. Cell. doi:10.1016/j.cell.2019.07.014

Modified CPP Targets Essential Readers in H3K27M-DIPG

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.


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)