Many sensory declines come along with aging, one of much concern being sight. That being said, there is a need for much more research on the visual changes associated with such aging. Specifically, the changes of rod bipolar cells and their ribbon synapses due to aging are an area of interest, along with the complex calcium systems at work. Using a zebrafish model, peptides help determine the effects of aging on vision and the retina.

TAMRA-RBP peptides tag rod bipolar cells

Zebrafish were used for this experiment thanks to their unique roles as model organisms; they share 70% genomic similarity with humans, and their short lifespan offers the chance to study life cycles in a few short years while still comparable to human aging over decades. Researchers compared data between middle-aged (MA, 18-months-old) and older-aged (OA, 36-months-old) zebrafish, equating to human ages of approximately 38 and 75 years of age, respectively. Using TAMRA ribbon-binding peptides from LifeTein, the team was able to observe changes between the two ages of zebrafish.

What was discovered was a decreased number of synaptic ribbons and increased ribbon length in the OA models. Further, there were many alterations to the local calcium dynamics of the system, implying a more complex change to vision deterioration than initially expected. The model shows how subtle changes could have vast implications for disease models where these alterations may be amplified, and surely sheds more light on how human vision may decline with age.

Abhishek P Shrestha, Nirujan Rameshkumar, Johane Martins Boff, Rhea Rajmanna, Thadshayini Chandrasegaran, Frederick E Courtney, David Zenisek, Thirumalini Vaithianathan
bioRxiv 2023.09.01.555825; doi: https://doi.org/10.1101/2023.09.01.555825

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Peptide Antagonist of F11R/JAM‑A Hinders Breast Cancer Metastasis

LifeTein’s CPPs used in Machine Learning

Enzyme-Degradable Peptides in Click Chemistry Drug Delivery

The most frequent diagnosed cancer in women as well as the leading cause of cancer death is breast cancer, with the worst subtype being triple-negative breast cancer (TNBC). While this subtype is the most likely to respond to chemotherapy, TNBC is also the most associated with metastasis to organs such as the brain, lungs, bones, and the liver. Research has found that increased F11R/JAM-A activity in TNBC and the transendothelial migration of the cancer cells, an initial step in metastasis. Researchers at the Medical University of Lodz, Poland began exploring the therapeutic possibilities of how the peptide antagonist of F11R/JAM‑A hinders breast cancer metastasis.

Antagonist Peptide hinders metastasis

LifeTein provided the group with the antagonistic P4D peptide designed, where they would test its effectiveness inhibiting F11R/JAM‑A. When administered in a model, P4D hindered the colony forming ability and proliferation of the TNBC breast cancer cell line. This then reduced the survival of TNBC cells due to the silencing and inhibition of F11R/JAM-A. This evidently hindered the metastasis in the mouse model used, meaning possible clinical trials could await the peptide in the future, or even the starting point of an chemically programmed antibody.

Bednarek, R., Wojkowska, D.W., Braun, M. et al. Triple negative breast cancer metastasis is hindered by a peptide antagonist of F11R/JAM‑A protein. Cancer Cell Int 23, 160 (2023). https://doi.org/10.1186/s12935-023-03023-4

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Convergent Evolution of Holocentromeres Studied with Peptides

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Enzyme-Degradable Peptides in Click Chemistry Drug Delivery

As methods of medicine advance, targeted drug delivery becomes a more appealing and achievable option over its non-selective counterpart. It can focus solely on increasing therapeutic concentration in the target area while greatly eliminating any exposure to healthy tissue, and thus drastically lowering side effects as well. The effective and simple mechanisms of click chemistry are a great way to design payloads for these targeted drug delivery methods. With the use of enzyme-degradable peptides in click chemistry drug delivery, lasting therapeutics can remain in the system for local sustained release over time as well.

Enzyme-degradable peptides for sustained drug delivery

The team at Rutgers focused on a two-phase method to set up the targeted drug delivery. First, ROS-sensitive PEGDA and acrylate-PEG-azide are aimed at the target area, driven by elevated free radical levels. Once the pretargeting is complete, a payload tethered to DBCO is delivered and captured via azide-DBCO reactions. Enzyme-degradable peptides were provided by LifeTein and incorporated into both steps for ongoing release of the captured payloads.

The results showed success in the models tested, with the initial dosage still effective in capturing the payload several days later. This system demonstrated the versatility of a two-phase method, where long term effects are even avoided further by the incorporation of enzyme degradable peptides. The proof of concept displayed here has great promise for the future of drug delivery, and just goes to show how applicable click chemistry is to even more fields.

Emily T. DiMartini, Kelly Kyker-Snowman & David I. Shreiber (2023) A click chemistry-based, free radical-initiated delivery system for the capture and release of payloads, Drug Delivery, 30:1, DOI: 10.1080/10717544.2023.2232952

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Convergent Evolution of Holocentromeres Studied with Peptides

LifeTein’s CPPs used in Machine Learning

HERV Peptide Derivatives as Biomarkers

During cell division, microtubules in the chromosome attach to a region called the centromere. While most species have a single size-restricted centromere, or a monocentromere, some species exist with multiple centromeres distributed across the chromosome, called holocentromeres. What is even more interesting is how holocentric chromosomes are considered to have evolved from the monocentric organisms, and this transition occurred independently across distant lineages, such as green algae, protozoans, invertebrates, as well as flowering plant families. One group aimed to study these holocentromeres more via the lilioid Chionographis japonica. Their goal was to better understand the convergent evolution of holocentromeres studied with peptides.

Peptides help explore holocentromeres

The group determined that the chromosomal localization of the target centromere is usually marked with histone H3 (CENH3). With this knowledge, they utilized peptides and antibodies of CENH3 provided by LifeTein to create models of the transition of C. japonica from interphase to prophase and study the possible mechanisms as well. They found the holocentromere was made up only of a few, evenly spaced CENH3-positive megabase-sized satellite arrays. Overall, the reason for the convergent evolution of holocentromeres from a monocentromere may stem from multiple factors, but more experiments like the ones presented will surely provide further analysis into this complex and fascinating case of convergent evolution.
Kuo, YT., Câmara, A.S., Schubert, V. et al. Holocentromeres can consist of merely a few megabase-sized satellite arrays. Nat Commun 14, 3502 (2023). https://doi.org/10.1038/s41467-023-38922-7

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MCA Fluorescent Peptides Measure Protease OMA1 Activity

Hydrogels Assembled from Short Peptides

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HERV Peptide Derivatives as Biomarkers

Tick infestations are a recurring roadblock of human development around the world, with estimated damages in the global economic landscape being as high as 30 billion USD. Specifically, India has long been susceptible to tick-borne diseases, due to multiple species invading the livestock. These regional parasites are major vectors for Crimean–Congo hemorrhagic fever virus (CCHFV), a disease with a devastating case fatality rate of 10–40%. While the main way of combatting the infestation of ticks and their carried disease has always been pesticides, often to an invasive degree of their own, scientists are working diligently for ways to produce a vaccine for this deadly and prevalent outbreak. One such method that has been explored is multi-epitopic peptide vaccines that combat Crimean–Congo hemorrhagic fever virus, specifically through the potential immune stimulatory responses they cause.

Multi-epitopic peptides help boost immune system

LifeTein provided the group with the two designed multi-epitopic peptides, VT1 and VT2. Using the two peptides, the group put them into two working vaccines in an effort to explore how effective they were at fighting back the ticks. With rabbits, they found strong immunity conferred by the vaccine, displayed by quick larval detachment, delayed tick feeding, low engorgement weights, and overall efficacy against both tick larvae and adults. The results show just how effective treatment with the vaccines are against ticks carrying CCHFV, and the compatibility with rabbits is a great starting point.

In an ideal experiment, the group would have tested on cattle, since that is a much more affected group by these ticks. Regardless, the suitability and stability displayed warrants more attention be put into these multi-epitopic peptide vaccines. Their efficacy displayed against infestations as such is sure to save the global economy billions, as well as countless lives. Immunization in this route is surely more appealing than that of constant and overwhelming pesticides being put in place at every conceivable turn. LifeTein is excited to see where else peptide-based vaccines can be implemented and what other unique properties they can bring to the table.

Nandi A, Manisha, Solanki V, Tiwari V, Sajjanar B, Sankar M, Saini M, Shrivastava S, Bhure SK, Ghosh S. Protective Efficacy of Multiple Epitope-Based Vaccine against Hyalomma anatolicum, Vector of Theileria annulata and Crimean–Congo Hemorrhagic Fever Virus. Vaccines. 2023; 11(4):881. https://doi.org/10.3390/vaccines11040881

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Antimicrobial Peptides Combat HLB

Hydrogels Assembled from Short Peptides

LifeTein’s CPPs used in Machine Learning

HERV Peptide Derivatives as Biomarkers

Cell-penetrating peptides (CPPs) are a longstanding part of the biochemical world, with their potential for delivering bioactive agents into cells, their importance will likely never diminish. However, not many advancements are being made to CPPs, rather scientists and teams alike are always looking to develop more efficient CPPs when possible. This is where a hot topic of recent comes into play, researchers utilized a deep-learning-based CPP prediction method, one they have named AiCPP, to effectively develop novel CPPs while reducing false-positive predictions. Using LifeTein cell-penetrating peptides and machine learning, AiCPP was able to combine data with other lists of CPPs to generate successful new sequences that the team at hand was able to test effectively.

LifeTein CPPs help train AI to generate new sequences

The group utilized a sliding window approach on their wealth of data and included a list of peptides with low similarity to CPPs as a negative to reduce false positives obtained. These techniques helped AiCPP stand out against other machine learning methods before it, and they found AiCPP can further optimize CPP sequences with higher efficacy as well. Valuable information can be gathered by studying the patterns by which this machine learning determines are effective for CPPs.

Though novel, the limitations of utilizing this and other machine-learning methods should be understood as well. Foremost, this and other CPP prediction studies do not answer any important questions about the mechanisms of cell permeation, or how each CPP specifically achieves this. It is also worth noting that the effectiveness of a given CPP is limited to the type of cell is it trying to penetrate, for example, MCF-7 used in the referenced study. Though, these shortcomings are possible to overcome, and in the future, AiCPP may become more advanced and be able to offer even more research, with LifeTein keeping up as well and ready to assist any team that may need their new CPPs developed.

Park H, Park J-H, Kim MS, Cho K, Shin J-M. In Silico Screening and Optimization of Cell-Penetrating Peptides Using Deep Learning Methods. Biomolecules. 2023; 13(3):522. https://doi.org/10.3390/biom13030522

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Hydrogels Assembled from Short Peptides

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HERV Peptide Derivatives as Biomarkers

Fibrin Hydrogels are a widely used material in regenerative medicine, often made with fibrinogen obtained from human plasma. However, this process can be very costly and have problems when used in other applications due to their limited mechanical properties. Researchers were interested in the prospect of composite hydrogels, made from the self-assembly of fibrinogen together with Fmoc-FF and Fmoc-RGD. Their results saw that these hydrogels co-assembled from short peptides and fibrin display biocompatibility, as well as the enhanced mechanical properties they were looking for.

Fibrin hydrogel enhanced with short peptide co-assembly

LifeTein provided the group with the essential peptides, Fmoc-FF and Fmoc-RGD, where the team tested different ratios of these peptides in combination with the fibrin precursor. Even from the naked eye alone, they could immediately tell the difference when the peptides were added in the presence of CaCl2. The resulting mixture displayed very favorable and biocompatible characteristics, even similar to the fibrin hydrogels it was replicating. The mixture could even jellify in situ, potentially allowing the pregel to be administered via injection

The protocol the group explored holds great potential for the future of regenerative medicine. Not only do they not cause any inflammatory response, but the possibilities still exist to modify these fibrin hydrogels for even further medicinal usage. The Fmoc-FF and Fmoc-RGD peptides used for the co-assembly of this hydrogel are commercially available, and companies like LifeTein are always ready to supply vital peptides like these to any groups researching to better our future.

Cristina Gila-Vilchez, Mari Carmen Mañas-Torres, Óscar Darío García-García, Alfredo Escribano-Huesca, Laura Rodríguez-Arco, Víctor Carriel, Ismael Rodriguez, Miguel Alaminos, Modesto Torcuato Lopez-Lopez, and Luis Álvarez de Cienfuegos
ACS Applied Polymer Materials 2023 5 (3), 2154-2165
DOI: 10.1021/acsapm.2c02164

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Self-Assembling Peptides on Graphite

LifeTein’s CPPs and Nanomaterial Internalization

HERV Peptide Derivatives as Biomarkers

Oncolytic viruses are a novel type of virus that specifically targets and eliminates tumor cells, and have been an emerging immunotherapy agent. One such is Coxsackievirus A21 (CVA21), which has been demonstrating a healthy safety profile as well as desired targeting of the cancerous cells. While producing drugs that can properly utilize this virus, there rises a need to characterize the ratio of total particles to empty ones, thus researchers developed a method to see Coxsackievirus A21 viral proteins quantified with capillary Western and peptides made up of the components of the capsid proteins.

CVA21 characterized with capillary Western and capsid peptides

LifeTein provided the group with the capsid peptides, VP1, VP2, VP3, and VP4, as well as the antibodies necessary for the testing. Results utilizing these peptides and antibodies included total particle concentration, empty particle concentration, as well as the empty to full ratio. Being able to characterize this kind of information in this downstream process will prove to be immensely valuable in future studies.

The Simple Western method displayed by the researchers proved itself to be an invaluable tool for optimizing decisions for these types of oncolytic virus studies. Consistency in these tests will surely lead to massive amounts of time being saved in future drug development and assessments. LifeTein will always be ready to lend a hand to any work needing peptides or antibodies to further their research in the broad field of drug application.

Paul F. Gillespie, Richard R. Rustandi, Andrew R. Swartz, Liang Shang, Jessica Raffaele, Ashley Prout, Nicholas Cunningham, Mohamed Dawod, James Z. Deng, Shiyi Wang, Jessica Olson, Yvonne Shieh, and John W. Loughney.
Quantitation of Coxsackievirus A21 Viral Proteins in Mixtures of Empty and Full Capsids Using Capillary Western.
Human Gene Therapy.Jan 2023.68-77.http://doi.org/10.1089/hum.2022.147

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HERV Peptide Derivatives as Biomarkers