scholarly journals Identification of peptides interfering the lrrk2/pp1 interaction

2019 ◽  
Author(s):  
Chang Zhi Dong ◽  
Heriberto Bruzzoni-Giovanell ◽  
Yanhua Yu ◽  
Karim Dorgham ◽  
Christophe Parizot ◽  
...  
Keyword(s):  
Biological Activity ◽  
Elisa Test ◽  
Short Peptides ◽  
Cell Penetrating Peptide ◽  
Original Sequence ◽  
Pathological Conditions ◽  
Cell Penetrating

ABSTRACTSerine/threonine phosphatases are responsible for counteracting the effect of the protein kinases implicated in the development of several pathologies. Here we identified by PEP-scan approach the sequence of a fragment of LRRK2, a Parkinson’s disease associated protein, interacting with the phosphatase PP1. The fragment, that is located in a LRRK2 domain of undefined function, was associated in N-terminal to an optimized cell penetrating peptide in order to study their in vitro and in vivo biological activity. From this original sequence, we developed and studied five interfering peptides (IPs) and identified two peptides able to disrupt the LRRK2/PP1 interaction by in vitro competition in anti-LRRK2 immunoprecipitates. Using FITC-labelled peptides, we confirmed the internalization of the peptides in cell lines as well as in and primary human normal and pathological cells. Finally, we have confirmed by ELISA test the association of Mut3DPT-LRRK2-Long and Mut3DPT-LRRK2-Short peptides to purified PP1 protein in a selective manner. The shortest peptides, MuteDPT-LRRK2-5 to 8 with either N or C-terminal deletions are not able neither disrupt the association LRRK2/PP1 nor to associate to purified PP1 protein. The peptides Mut3DPT-LRRK2-Long and Mut3DPT-LRRK2-Short may be new tools to study the role of LRRK2/PP1 interaction in normal and pathological conditions.

“In vivo” amplification of biological activity of tetragastrin by amino acid hydroxamates

1984 ◽  
Vol 4 (12) ◽  
pp. 1009-1015 ◽  
Author(s):  
J. P. Bali ◽  
H. Mattras ◽  
A. Previero ◽  
M. A. Coletti-Previero
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Aromatic Amino Acid ◽  
Aminopeptidase Activity ◽  
Proteolytic Degradation ◽  
Short Peptides ◽  
Rat Blood ◽  
Active Peptides

Rat blood was shown to contain an aminopeptidase which rapidly hydrolyses short peptides containing an aromatic amino acid as N-terminal residue. Using tetragastrin (Trp-Met-Asp-PheNH 2) as substrate, we showed that some amino acid hydroxamates inhibit rat aminopeptidase activity ‘in vitro’ in the following order: HTrpNHOH > HPheNHOH ≫ HAIaNHOH. The same hydroxamates markedly enhanced the biological activity of tetragastrin ‘in vivo’. The amplification of the secretory effect, correlated with the amount of the hydroxamate used, strongly suggests that these compounds can stabilize a number of active peptides in vivo by inhibiting their proteolytic degradation.

scholarly journals The anticancer efficacy of paclitaxel liposomes modified with low-toxicity hydrophobic cell-penetrating peptides in breast cancer: an in vitro and in vivo evaluation

RSC Advances ◽  
2018 ◽  
Vol 8 (43) ◽  
pp. 24084-24093 ◽  
Author(s):  
Qi Zhang ◽  
Jing Wang ◽  
Hao Zhang ◽  
Dan Liu ◽  
Linlin Ming ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Delivery ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
In Vivo Evaluation ◽  
Anticancer Efficacy ◽  
Cell Penetrating ◽  
Low Toxicity

Hydrophobic cell penetrating peptide PFVYLI-modified liposomes have been developed for the targeted delivery of PTX into tumors.

scholarly journals THE BIOLOGICAL ACTIVITY OF EUROPEAN MISTLETOE (Viscum album) EXTRACTS AND THEIR PHARMACEUTICAL IMPACT

1970 ◽  
Vol 63 ◽  
Author(s):  
Simona Ioana Vicaş ◽  
Carmen Socaciu
Keyword(s):  
Biological Activity ◽  
Mechanism Of Action ◽  
Viscum Album ◽  
Cancer Therapies ◽  
Main Principle ◽  
Mistletoe Extracts ◽  
Comparison Of The Results

Extracts of Viscum album (mistletoe) are widely used as complementary cancer therapies in Europe. The mistletoe lectins and viscotoxins have been identified as the main principle of mistletoe extracts that participating in biological activity of V. album. These compounds were isolated and studied in vitro and in vivo for their biological activity and mechanism of action. A comparison of the results to those using whole extracts indicated that lectins and viscotoxins are not the only bioactive compounds present in the mistletoe. In this paper, we review the recent studies regarding with cytotoxic activity on tumor cells of mistletoe extracts, as well as, the role of this semiparasitic plant in diabetics and hypertension illness.

scholarly journals Efficient intracellular delivery of proteins by a multifunctional chimaeric peptide in vitro and in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Siyuan Yu ◽  
Han Yang ◽  
Tingdong Li ◽  
Haifeng Pan ◽  
Shuling Ren ◽  
...  
Keyword(s):  
Protein Delivery ◽  
Leucine Zipper ◽  
Endosomal Escape ◽  
Cell Penetrating Peptide ◽  
Macromolecular Drugs ◽  
Cell Penetrating ◽  
In Series ◽  
Factor Α

AbstractProtein delivery with cell-penetrating peptide is opening up the possibility of using targets inside cells for therapeutic or biological applications; however, cell-penetrating peptide-mediated protein delivery commonly suffers from ineffective endosomal escape and low tolerance in serum, thereby limiting in vivo efficacy. Here, we present an intracellular protein delivery system consisting of four modules in series: cell-penetrating peptide, pH-dependent membrane active peptide, endosome-specific protease sites and a leucine zipper. This system exhibits enhanced delivery efficiency and serum tolerance, depending on proteolytic cleavage-facilitated endosomal escape and leucine zipper-based dimerisation. Intravenous injection of protein phosphatase 1B fused with this system successfully suppresses the tumour necrosis factor-α-induced systemic inflammatory response and acetaminophen-induced acute liver failure in a mouse model. We believe that the strategy of using multifunctional chimaeric peptides is valuable for the development of cell-penetrating peptide-based protein delivery systems, and facilitate the development of biological macromolecular drugs for use against intracellular targets.

scholarly journals Potassium channels, megapolarization, and water pore formation are key determinants for cationic cell-penetrating peptide translocation into cells

2020 ◽  
Author(s):  
Evgeniya Trofimenko ◽  
Gianvito Grasso ◽  
Mathieu Heulot ◽  
Nadja Chevalier ◽  
Marco A. Deriu ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Pore Formation ◽  
Transmembrane Potential ◽  
Cellular Membrane ◽  
Cell Penetrating Peptides ◽  
Bioactive Molecules ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating

SummaryCell-penetrating peptides (CPPs) allow intracellular delivery of cargo molecules. CPPs provide efficient methodology to transfer bioactive molecules in cells, in particular in conditions when transcription or translation of cargo-encoding sequences is not desirable or achievable. The mechanisms allowing CPPs to enter cells are ill-defined and controversial. This work identifies potassium channels as key regulators of cationic CPP translocation. Using a CRISPR/Cas9-based screening, we discovered that KCNQ5, KCNN4, and KCNK5 positively modulate CPP cellular direct translocation by reducing transmembrane potential (Vm). Cationic CPPs further decrease the Vm to megapolarization values (about −150 mV) leading to the formation of ∼2 nm-wide water pores used by CPPs to access the cell’s cytoplasm. Pharmacological manipulation to lower transmembrane potential boosted CPPs cellular uptake in zebrafish and mouse models. Besides identifying the first genes that regulate CPP translocation, this work characterizes key mechanistic steps used by CPPs to cross cellular membrane. This opens the ground for pharmacological strategies augmenting the susceptibility of cells to capture CPP-linked cargos in vitro and in vivo.

scholarly journals Microbial Metabolites of Flavan-3-Ols and Their Biological Activity

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2260 ◽  
Author(s):  
Campos ◽  
Stehle ◽  
Simon
Keyword(s):  
Biological Activity ◽  
Scientific Literature ◽  
Current Status ◽  
Microbial Metabolites ◽  
Potential Health ◽  
In Vivo Animal Models ◽  
Polyphenol Intake

Flavan-3-ols are the main contributors to polyphenol intake. Many varying beneficial health effects in humans have been attributed to them, including the prevention of cardiovascular disease and cancer. Nevertheless, the mechanisms by which these flavonoids could exert beneficial functions are not entirely known. Several in vitro studies and in vivo animal models have tried to elucidate the role of the specific colonic metabolites on the health properties that are attributed to the parent compounds since a larger number of ingested flavan-3-ols reach the colon and undergo there microbial metabolism. Many new studies about this topic have been performed over the last few years and, to the best of our knowledge, no scientific literature review regarding the bioactivity of all identified microbial metabolites of flavan-3-ols has been recently published. Therefore, the aim of this review is to present the current status of knowledge on the potential health benefits of flavan-3-ol microbial metabolites in humans while using the latest evidence on their biological activity.

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