Glioblastoma (GBM) is the most commonly occurring terminal brain cancer. Due to complications in the brain like the blood brain barrier, methods of treating GBM are few and far between. Therefore, treatment in the region is generally left to specific chemotherapeutics like temozolomide (TMZ), which has the unique capability to bypass the brain blood barrier. However, matters become more complicated as many subpopulations of GBM, namely the glioma stem cell populations, are resistant to TMZ. Researchers are looking into ways to bypass this resilience, namely connexin 43 (Cx43) hemichannels that when inhibited by mimetic peptides allow the glioma stem cell populations to be treated significantly more effectively by TMZ
Cx43 mimetic peptides weaken cancer’s resistance to TMZ
Researchers used LifeTein’s peptide synthesis service to create two mimetic peptides of Cx43, αCT11 and αCT1, to inhibit Cx43 hemichannels and then sensitize the glioma cells and other GBM cell populations to TMZ in a 3D hyaluronic acid and collagen hydrogel-based tumor organoid system. After testing this model extensively, the group found that only the αCT1 peptide in combination with TMZ proved effective in treating the cell lines. It is believed that the αCT1 is more successful due to its cell penetrating sequence when compared to αCT11.
Overall, the group emphasizes that the model used does not accurately mimic the cellular heterogeneity of GBM, but the results are a fantastic start and can be used as a tool to further study treatment of this aggressive brain cancer. Further work can optimize this treatment and can hopefully provide a chance for those who have to go against this fatal ailment.
Jingru Che, Thomas J. DePalma, Hemamylammal Sivakumar, et al. αCT1 Peptide Sensitizes Glioma Cells to Temozolomide in a Glioblastoma Organoid Platform. Authorea. April 29, 2022.
Zonula occludens toxin (Zot) and its biologically active fragment, delta G, have been shown to reversibly open tight junctions (TJ) in endothelial and epithelial cells. AT1002, a six-mer synthetic peptide H-FCIGRL-OH of ZO toxin was identified and synthesized that retains the Zot permeating effect on intercellular TJ. It was found that AT1002 disrupts the epithelial barrier while larazotide acetate restores barrier function by rearrangement of actin. In addition, AT1002 enhances the transport of molecular weight markers or agents with low bioavailability with no cytotoxicity. So this synthetic peptide AT1002 is a tight junction modulator with promising permeation-enhancing activity.
A Synthetic Peptide Showed Enhanced Nasal Drug Delivery
The C-terminal amidated AT1002 FCIGRL-NH2 showed enhanced nasal drug delivery and may lead to the development of a practical drug delivery technology for drugs with low bioavailability.
The synthetic peptide AT1002 was synthesized by LifeTein.
The SrtA substrates Biotin–aminohexanoic acid–LPETGS and SELPETGG were used for the interactions between immune cells ‘Labelling Immune Partnerships by SorTagging Intercellular Contacts’ (LIPSTIC). The peptide-receptor interactions enable the direct measurement of dynamic cell–cell interactions. The peptides are flexible tools for use with different receptor–ligand pairs and a range of detectable labels.
LifeTein is unveiling an expedited peptide synthesis program, promising to place peptides in its customers’ hands within 3-5 business days. The RushPep™ peptide synthesis service was designed to circumvent the existing limitations of conventional solid-phase peptide synthesis (SPPS), which involves a long coupling time and low yield. RushPep™ shortens the time needed for individual coupling, deprotection and washing steps. The proprietary methodology renders processing ten times faster than in classical synthesis while simultaneously circumventing the limitations caused by the formation of by-products or intermediates to which traditional SPPS approaches are subject.
LifeTein’s Rush Custom Peptide Synthesis Service
“When designing the RushPep™ methodology, our focus was to not only to produce peptides of high quality and purity but also to offer a streamlined solution that would increase the efficiency of researchers’ protein discovery workflows,” stated Dr. Ya Chen, Head of LifeTein’s Rush Peptide Synthesis Group. “RushPep™ achieves these goals by synthesizing the peptides in 3–5 business days to accelerate research and discovery.”
Chen continued, “The reliability of RushPep™ rush peptide synthesis ensures that the peptides are finished in 3–5 business days with high-batch-to-batch reproducibility. ” Most of the crude peptides have a purity of over 80%. RushPep™ peptide service is valuable for the scientists and researchers because it allows them to finish their proteomics projects in a fast and cost-efficient manner.
The anti-apoptotic factor Bcl-2 is over-expressed in B-cell lymphoma cells as their main survival mechanism by binding to IP3R2 on endoplasmic reticulum (ER). In this study, a cell-penetrating version of BIRD-2 peptide (Bcl-2/IP3R Disrupter-2 peptide with a TAT sequence) made by LifeTein was used to break up the complex formed by Bcl-2 and IP3R2 in human diffuse large B-cell lymphoma (DLBCL) cells. Ca2+ signaling-related events are suggested to be the killing mechanism of BIRD-2 peptide on DLBCL cells.
Some cell-permeable peptides are able to carry cargos across cell membrane even without any covalent links. Biotinylated peptides, including L- and D-TAT peptides made by LifeTein were used in this study to show that two types of cell surface receptors, heparan sulfate proteoglycans and Neuropilin-1, play critical roles in the delivery of silver-based nanoparticles into cells by cell-permeable peptides.
A tumor-penetrating peptide, iRGD, was synthesized by LifeTein. It was found that iRGD improves tumor-specific penetration of intraperitoneal compounds and enhances intraperitoneal chemotherapy (IPC) in mice. This penetration was tumor-specific. When the fluorescein was attached to iRGD and mixed with nanoparticles, the mixture could penetrate into fresh human peritoneal metastasis explants. The evidence proved that the LifeTein iRGD enhanced intratumoral entry. The intraperitoneal iRGD co-administration is a simple and effective strategy to facilitate tumor detection and potential application for the therapeutic improvement.
Anti-inflammatory peptides were isolated from alcalase hydrolysates out of tuna cooking juice by-product. Synthetic peptides from LifeTein were used to confirm the inhibitory anti-inflammatory activity. The amino acid sequences of the two anti-inflammatory peptides isolated from AH hydrolysates were Pro-Arg-Arg-Thr-Arg-Met-Met-Asn-Gly-Gly-Arg (1543.8 Da) and Met-Gly-Pro-Ala-Met-Met-Arg-Thr-Met-Pro-Gly (1211.5 Da).
Peptide scanning involves the chemical synthesis of overlapping peptides covering the antigen sequence targeted by the investigated antibodies. Peptide truncations are used to further narrow down the epitope sequence and mutagenesis of each amino acid such as alanine substitution can also indicate the binding affinity. Cross-reactive epitopes were found in Borrelia burgdorferi p66.
Cross-reactive epitopes in Borrelia burgdorferi p66, Clinical and Vaccine Immunology, 2015
Cell-penetrating peptides (CPPs) have the ability to enter a cell’s plasma membrane independent of a membrane receptor. Attached to a CPP, therapeutic cargo could be delivered to an intracellular target, thus overcoming the entry restrictions set by the plasma membrane.
Peptide Synthesis & Cell Penetration
The cationic CPPs interact with negatively charged head groups of lipids directly in the plasma membrane through electrostatic interactions. The increased local peptide concentration at the membrane surface will cause a transient destabilization of the lipid bilayer and lead to cell entry. The hydrophobic interactions, especially facilitated by the presence of tryptophan residues, may be important for the CPP-membrane interaction and cellular internalization.