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 Peptides Help Broaden Our Understanding of Engineering Physicochemical Properties onto Nanoparticles

LifeTein’s cysteine-containing peptides helped researchers better understand the effect peptide physicochemical properties have on the pharmacokinetic profiles of the nanoparticles they are attached to. Better understanding and control of these effects is invaluable for future engineering design of many types of therapeutic nanomaterials, including for treatment of traumatic brain injuries (TBI).

Nanoparticles’ Physicochemical Properties Influenced by Peptides

Scientists at the University of California were keen on finding out what exact physicochemical properties in peptides affect the pharmacokinetics of nanoparticles designed for treating TBI. Nanoparticles are a convenient means of therapeutic drug delivery, as they can exhibit different pharmacokinetic profiles from the drug cargo in their core. This experiment analyzed how functionalizing the nanoparticles with PEG and an array of peptides with varying physicochemical properties, provided by LifeTein, contribute to the biodistribution in vivo, using a mouse model of TBI.

Results showed that the biodistribution of the modified nanoparticles varied mainly as a result of the charge of the peptides attached; basic peptides resulted in restricted distributions in the brain via convection-enhanced delivery (CED), as well as elevated off-target organ accumulation resulting in a decrease in brain accumulation when using systemic administration. In comparison, nanoparticles modified with acidic, zwitterionic, or neutral peptides demonstrated less restricted distribution in the brain via CED, and increased accumulation in injured vs. uninjured brain tissue after systemic administration.

This study suggests that the charge of peptides should be greatly taken into account when designing nanoparticles with peptide-modified surfaces. Peptides offer a great way to influence the biological interactions of nanoparticles, and understanding what physicochemical properties contribute to said influence will further advance the use of therapeutic nanoparticles in treatments like TBI.

Reference: Waggoner, L.E., Madias, M.I., Hurtado, A.A. et al. Pharmacokinetic Analysis of Peptide-Modified Nanoparticles with Engineered Physicochemical Properties in a Mouse Model of Traumatic Brain Injury. AAPS J 23, 100 (2021). https://doi.org/10.1208/s12248-021-00626-5

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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 Synthesized Peptides of Six Phosphorylations Using Microwave-Assisted Heating Technology

Phosphorylation plays a vital role in the regulation of cellular processes. Each phosphorylation pattern leads to different interactions and could result in distinct biological outcomes.

Single phosphorylated peptides are frequently used for research. However, multi-site phosphorylations play a more important role in protein-protein interaction, nuclear import and export, and many other functions.

The monophosphorylated peptides are much easier to synthesize than multiphosphorylated peptides using traditional methods. There are many reasons for the difficulties. First of all, the steric hindrance of the protected phosphorylated amino acids would decrease the coupling yield. In addition, the protecting group and cleavage conditions are very harsh for conventional methods.

LifeTein adapted the microwave-assisted heating technology for multiphosphorylated peptide synthesis. Our method increases the coupling efficiency with good yields. In our study, we utilized the optimized conditions for synthesizing peptides containing six phosphorylated amino acids.

Chemical peptide synthesis allows the preparation of multi phosphorylation peptides with specific required patterns and can be used to elucidate the function of each
modification for drug target screening

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)

BRAF Peptide Inhibitors By LifeTein Target the Dimer Interface of BRAF

BRAF is the most frequently mutated kinase in human cancers and is one of the major effectors of oncogenic RAS. So BRAF is a target of interest for anti-cancer drug development.

Two FDA-approved inhibitors, dabrafenib and vemurafenib have been developed as inhibitors for BRAF. These ATP-competitive inhibitors potently inhibit the most common BRAF variant V600E. However, current BRAF inhibitors could induce drug resistance and paradoxical activation. New approaches and drug candidates are needed to disrupt the intact dimer interface of BRAF. The 10-mer peptide inhibitor braftide was designed using a computational approach to block RAF dimerization. It was found that the peptide inhibitor triggers selective protein degradation of BRAF and MEK through proteasome-mediated protein degradation in cells.

The combination of ATP competitive inhibitors and braftide eliminates paradoxical activation. This alternative strategy will improve the efficacy of current ATP-competitive inhibitors. The RAF dimer interface could be a promising therapeutic target.

Braftide is a 10-mer peptide TRHVNILLFM. Braftide disrupts BRAF dimers and inhibits BRAF kinase activity. Braftide causes degradation of BRAF leading to destabilized MAPK complexes. Braftide synergizes with ATP-competitive inhibitors like Dabrafenib to mitigate paradoxical MAPK activation and downregulate MAPK signaling.

In this study, the Braftide, Null-Braftide, TAT-PEGlinker-Braftide, and TAT peptides were purchased from LifeTein with TFA removal.

Reference: ACS Chem Biol. 2019 Jul 19; 14(7): 1471–1480.

BRAF Peptide Inhibitors Targeting the Dimer Interface of BRAF

LifeTein synthesized a long peptide of 75 residues: C subunit of the ATP synthase

LifeTein synthesized the C subunit of the ATP synthase. The c subunit is a highly hydrophobic peptide of 75 residues. This is a transmembrane α-helical “hairpin” localized in the mitochondrial inner membrane where it assembles into oligomers of 8–16 units depending on the species.

The long peptide of the C subunit spontaneously folds into a β‑sheet conformation. This was confirmed by the peptide’s far-UV circular dichroism (CD) spectrum. The c subunit in β-sheet conformation could form aggregates. The formation of cross-β aggregates was monitored using the amyloid-binding dye Tiofavin T (TT). It was found that a critical role for Ca2+ in the folding and self-assembly of c subunits into oligomers rather than fibrils.

The amyloidogenic peptides can form ion channels in lipid bilayers. The human unmodified synthetic c subunit is an amyloidogenic peptide and its oligomers
are capable of forming ion-conducting pores in planar lipid bilayers. Similarly, amyloid and synuclein in their oligomeric conformations can form ion channels in planar lipid bilayers with lower conductances compared to the canonical PTP. These toxic forms of misfolded c subunit might play a significant role in cell pathophysiology.

Reference: https://www.nature.com/articles/s41598-021-88157-z.pdf

Long Peptide Synthesis of C Subunit

Rabbit Polyclonal Anti-gM and Anti-gN Antibodies Using Synthetic Long Peptides

Human cytomegalovirus (HCMV) is currently a major cause of congenital disease in newborns and organ failure in transplant recipients. Various vaccine strategies have been developed, including live attenuated, recombinant viral proteins, dense bodies, vector vaccine subunit, or synthetic peptide epitopes. The rabbit polyclonal anti-gM and anti-gN antibodies were elicited by vaccinating animals with synthesized peptide sequences of gM (1-13aa and 345-372aa) and gN (61-101aa). Animal immunization and sera collection were performed at Lifetein, LLC (Hillsborough, NJ, USA). The sera were affinity-purified by its corresponding peptides.

These formulations have been extensively tested using different animal models and have shown promising immunogenicity and protective efficacy. Some of these strategies have already progressed to clinical trials with humans. The study was studied by Vaccine Analytical Research Development and Vaccine Process Development Merck & Co., Inc., Kenilworth, NJ, USA.

Synthetic Long Peptides