Peptides for Parkinson’s disease (PD)

All peptides used in this study for Parkinson’s disease were synthesized by LifeTein. The α-synuclein is an indication in the pathogenesis of Parkinson’s disease. It was found that a molecular mimicry mechanism between HSV1 and human α-synuclein could trigger PD.

Journal of Neuroimmunology, doi:10.1016/j.jneuroim.2016.01.007 Humoral cross reactivity between α-synuclein and herpes simplex − 1 epitope in Parkinson’s disease, a triggering role in the disease?

How does BIRD-2 peptide kill B-cell lymphoma?

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.

[PDF] Inhibiting Bcl-2 via its BH4 domain in DLBCL cancers to provoke pro-apoptotic Ca2+ signaling

Look Who’s Talking

Intraspecies pheromone signaling regulated by proteases is critical for fungi procreation.  The fungal aspartyl protease Bar1 was shown to have unique substrate specificity of important implications in fungal evolution.  LifeTein synthesized substrate peptides of Bar1, dual-tagged with DABCYL and EDANS, from the sequence of α pheromone, the native target of Bar1. Referred as internally quench or IQ peptides, they were used in fluorescence resonance energy transfer (FRET) assays to study the enzyme kinetics of Bar1.

mBio 6(6):e01604-15. doi:10.1128/mBio.01604-15. Evolutionary selection on barrier activity: Bar1 is an aspartyl protease with novel substrate specificity.

A New Patent Using Peptides

A patent has been published that describes new methods of manipulating plant stomatal development through artificially controlling how CRSP is expressing in plant cells.  The cleavage of epidermal patterning factor 2 (EPF2) by a serine protease CRSP is a key regulating mechanism in plant stomatal development.  A 30-mer EPF2 peptide, dual-tagged with DABCYL and EDANS, was synthesized by LifeTein to evaluate the protease activity of synthetic CRSP in a FRET assay.

Compositions and methods for mediating plant stomatal development in response to carbon dioxide and applications for engineering drought tolerance in plants.

Nanoparticles Get Help from Cell-Penetrating Peptides

Some cell-penetrating 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-penetrating peptides.

Science Advances 06 Nov 2015: Vol. 1, no. 10, e1500821 DOI: 10.1126/sciadv.1500821.  Neuropilin-1 and heparan sulfate proteoglycans cooperate in cellular uptake of nanoparticles functionalized by cationic cell-penetrating peptides.

Predicting type 1 diabetes in children

MAP is a pathogenic bacterium infecting livestock and found prevalent in dairy products.  Because some of its proteins are sequentially homologous to human zinc transporter 8 (ZnT8) protein and proinsulin (PI), children could develop autoimmunity against ZnT8 and PI after being exposed to MAP in dairy foods, and generating antibodies against MAP, and might subsequently develop type I diabetes.  The hypothesis was tested by using ZnT8, PI and MAP peptides synthesized by LifeTein to assess the cross-reactivity of antibodies in sera samples from at-risk children.

Journal of Diabetes Research, Article ID 5842701, in press. Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies.

Improving Antibody Therapy For Colorectal Cancer

The therapeutic monoclonal antibody cetuximab is among the latest arsenal developed for war on cancer, designed to block tumor growth by specifically targeting the extracellular domain of EGFR on the surface of cancer cells.  Alarmingly, resistance to cetuximab has been observed.  Using peptides containing methylated arginine residues synthesized by LifeTein to generated specific antibodies in mice, the researchers were able to pinpoint Arg198 and Arg200 of EGFR were methylated by protein arginine methyltransferase 1 (PRMT1) in colorectal cancer cells, which could be critical for cetuximab resistance.  Their results paved a way for developing better treatment for cancer patients.

The Journal of Clinical Investigation. 2015;125(12):4529-4543. doi:10.1172/JCI82826. PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response.

To Make Simpler and Better Biosensors

In order to improve the design of immunosensors, fluorophores were conjugated on to the single chain Fv (scFv) fragment of a recombinant anti-BGP antibody to form Quenchbodies (Q-bodies), in which their fluorescence is internally quenched by Trp residues of scFv.  Unlabeled and biotinylated BGP peptides made by LifeTein were used in ELISA and FRET assays as the ligand to evaluate the quality of Qbodies, and to demonstrate the antigen-dependent fluorescence of Qbodies.

ACS Sensors, Article ASAP. DOI: 10.1021/acssensors.5b00089.  Q-Bodies from Recombinant Single-Chain Fv Fragment with Better Yield and Expanded Palette of Fluorophores.

A tumor-penetrating peptide iRGD by LifeTein targets peritoneal carinomatosis

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.

A tumor-penetrating peptide enhances circulation-independent targeting of peritoneal carcinomatosis, Journal of Controlled Release, Volume 212, 28 August 2015, Pages 59–69