Luminescent Peptide Labeling Based on a Histidine-Binding Iridium(III) Complex for Cell Penetration and Intracellular Targeting Studies

2011 ◽  
Vol 17 (29) ◽  
pp. 8028-8032 ◽  
Author(s):  
Xiaobo Wang ◽  
Junli Jia ◽  
Zezhu Huang ◽  
Ming Zhou ◽  
Hao Fei
Keyword(s):  
Cell Penetration ◽  
Intracellular Targeting ◽  
Peptide Labeling

Three-Dimensional Structure of Rotavirus-Fab Complex

1990 ◽  
Vol 48 (1) ◽  
pp. 238-239
Author(s):  
B.V.V. Prasad ◽  
E. Marietta ◽  
J.W. Burns ◽  
M.K. Estes ◽  
W. Chiu
Keyword(s):  
Image Processing ◽  
Smooth Surface ◽  
Three Dimensional ◽  
Outer Shell ◽  
Dimensional Structure ◽  
Structural Studies ◽  
Cell Penetration ◽  
Electron Cryomicroscopy ◽  
Image Processing Techniques ◽  
Processing Techniques

Rotaviruses are spherical, double-shelled particles. They have been identified as a major cause of infantile gastroenteritis worldwide. In our earlier studies we determined the three-dimensional structures of double-and single-shelled simian rotavirus embedded in vitreous ice using electron cryomicroscopy and image processing techniques to a resolution of 40Å. A distinctive feature of the rotavirus structure is the presence of 132 large channels spanning across both the shells at all 5- and 6-coordinated positions of a T=13ℓ icosahedral lattice. The outer shell has 60 spikes emanating from its relatively smooth surface. The inner shell, in contrast, exhibits a bristly surface made of 260 morphological units at all local and strict 3-fold axes (Fig.l).The outer shell of rotavirus is made up of two proteins, VP4 and VP7. VP7, a glycoprotein and a neutralization antigen, is the major component. VP4 has been implicated in several important functions such as cell penetration, hemagglutination, neutralization and virulence. From our earlier studies we had proposed that the spikes correspond to VP4 and the rest of the surface is composed of VP7. Our recent structural studies, using the same techniques, with monoclonal antibodies specific to VP4 have established that surface spikes are made up of VP4.

A Novel Amino Acid Sequence-based Computational Approach to Predicting Cell-penetrating Peptides

2019 ◽  
Vol 15 (3) ◽  
pp. 206-211 ◽  
Author(s):  
Jihui Tang ◽  
Jie Ning ◽  
Xiaoyan Liu ◽  
Baoming Wu ◽  
Rongfeng Hu
Keyword(s):  
Machine Learning ◽  
Amino Acid ◽  
Amino Acid Position ◽  
Cell Penetrating Peptides ◽  
Support Vector ◽  
Cell Penetration ◽  
Drug Candidates ◽  
Machine Learning Model ◽  
Cell Penetrating ◽  
Novel Method

<P>Introduction: Machine Learning is a useful tool for the prediction of cell-penetration compounds as drug candidates. </P><P> Materials and Methods: In this study, we developed a novel method for predicting Cell-Penetrating Peptides (CPPs) membrane penetrating capability. For this, we used orthogonal encoding to encode amino acid and each amino acid position as one variable. Then a software of IBM spss modeler and a dataset including 533 CPPs, were used for model screening. </P><P> Results: The results indicated that the machine learning model of Support Vector Machine (SVM) was suitable for predicting membrane penetrating capability. For improvement, the three CPPs with the most longer lengths were used to predict CPPs. The penetration capability can be predicted with an accuracy of close to 95%. </P><P> Conclusion: All the results indicated that by using amino acid position as a variable can be a perspective method for predicting CPPs membrane penetrating capability.</P>

scholarly journals Antimicrobial and Amyloidogenic Activity of Peptides Synthesized on the Basis of the Ribosomal S1 Protein from Thermus Thermophilus

2020 ◽  
Vol 21 (17) ◽  
pp. 6382 ◽  
Author(s):  
Stanislav Kurpe ◽  
Sergei Grishin ◽  
Alexey Surin ◽  
Olga Selivanova ◽  
Roman Fadeev ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Thermus Thermophilus ◽  
Antibacterial Properties ◽  
Cell Penetration ◽  
Research Directions ◽  
Bacterial Proteins ◽  
Hiv Transcription ◽  
Parent Protein ◽  
Amyloidogenic Peptides ◽  
New Research

Controlling the aggregation of vital bacterial proteins could be one of the new research directions and form the basis for the search and development of antibacterial drugs with targeted action. Such approach may be considered as an alternative one to antibiotics. Amyloidogenic regions can, like antibacterial peptides, interact with the “parent” protein, for example, ribosomal S1 protein (specific only for bacteria), and interfere with its functioning. The aim of the work was to search for peptides based on the ribosomal S1 protein from T. thermophilus, exhibiting both aggregation and antibacterial properties. The biological system of the response of Gram-negative bacteria T. thermophilus to the action of peptides was characterized. Among the seven studied peptides, designed based on the S1 protein sequence, the R23I (modified by the addition of HIV transcription factor fragment for bacterial cell penetration), R23T (modified), and V10I (unmodified) peptides have biological activity that inhibits the growth of T. thermophilus cells, that is, they have antimicrobial activity. But, only the R23I peptide had the most pronounced activity comparable with the commercial antibiotics. We have compared the proteome of peptide-treated and intact T. thermophilus cells. These important data indicate a decrease in the level of energy metabolism and anabolic processes, including the processes of biosynthesis of proteins and nucleic acids. Under the action of 20 and 50 μg/mL R23I, a decrease in the number of proteins in T. thermophilus cells was observed and S1 ribosomal protein was absent. The obtained results are important for understanding the mechanism of amyloidogenic peptides with antimicrobial activity and can be used to develop new and improved analogues.

scholarly journals Synthesis and Characterization of a Fullerenol Derivative for Potential Biological Applications

2020 ◽  
Vol 4 (1) ◽  
pp. 15
Author(s):  
Eduardo Ravelo-Nieto ◽  
Alvaro Duarte-Ruiz ◽  
Luis H. Reyes ◽  
Juan C. Cruz
Keyword(s):  
Phase Transfer ◽  
Protein A ◽  
Structural Features ◽  
Cellular Level ◽  
Cellulose Membrane ◽  
Cell Penetration ◽  
Covalent Functionalization ◽  
Dialysis Tubing ◽  
Surface Functionality

Several biological barriers are generally responsible for the limited delivery of cargoes at the cellular level. Fullerenols have unique structural features and possess suitable properties for interaction with the cells. This study aimed to synthesize and characterize a fullerenol derivative with desirable characteristics (size, charge, functionality) to develop cell penetration vehicles. Fullerenol was synthesized from fullerene (C60) solubilized in toluene, followed by hydroxylation with hydrogen peroxide and tetra-n-butylammonium hydroxide (TBAH) as a phase transfer catalyst. The obtained product was purified by a Florisil chromatography column (water as the eluent), followed by dialysis (cellulose membrane dialysis tubing) and freeze-drying (yield 66%). Subsequently, a silane coupling agent was conjugated on the fullerenol surface to render free amine functional groups for further covalent functionalization with other molecules. Characterization via UV–VIS, FTIR-ATR, Raman, DLS, and SEM techniques was conducted to evaluate the composition, size, morphology, surface functionality, and structural properties. We are currently working on the conjugation of the potent cell-penetrating agents Buforin II (BUFII) and the Outer Membrane Protein A (OmpA) on the surface of the fullerenol to estimate whether cell penetration and endosome escape are improved concerning conventional polymeric vehicles and our previous developments with iron oxide nanoparticles.

scholarly journals Cell penetration efficiency analysis of different atomic force microscopy nanoneedles into living cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marcos Penedo ◽  
Tetsuya Shirokawa ◽  
Mohammad Shahidul Alam ◽  
Keisuke Miyazawa ◽  
Takehiko Ichikawa ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
Cell Membrane ◽  
Cell Biology ◽  
Cell Damage ◽  
Efficiency Analysis ◽  
Living Cells ◽  
Biomolecular Recognition ◽  
Cell Penetration ◽  
Force Microscopy ◽  
Atomic Force

AbstractOver the last decade, nanoneedle-based systems have demonstrated to be extremely useful in cell biology. They can be used as nanotools for drug delivery, biosensing or biomolecular recognition inside cells; or they can be employed to select and sort in parallel a large number of living cells. When using these nanoprobes, the most important requirement is to minimize the cell damage, reducing the forces and indentation lengths needed to penetrate the cell membrane. This is normally achieved by reducing the diameter of the nanoneedles. However, several studies have shown that nanoneedles with a flat tip display lower penetration forces and indentation lengths. In this work, we have tested different nanoneedle shapes and diameters to reduce the force and the indentation length needed to penetrate the cell membrane, demonstrating that ultra-thin and sharp nanoprobes can further reduce them, consequently minimizing the cell damage.

Novel Glutamine Antagonist JHU395 Suppresses MYC-Driven Medulloblastoma Growth and Induces Apoptosis

2021 ◽  
Author(s):  
Khoa Pham ◽  
Micah J Maxwell ◽  
Heather Sweeney ◽  
Jesse Alt ◽  
Rana Rais ◽  
...  
Keyword(s):  
Pediatric Brain Tumor ◽  
Glutamine Metabolism ◽  
Rank Test ◽  
Cell Penetration ◽  
Plasma Ratio ◽  
Log Rank Test ◽  
Naturally Occurring ◽  
Ongoing Development ◽  
Orthotopic Xenografts ◽  
Pediatric Brain

Abstract Medulloblastoma is the most common malignant pediatric brain tumor. Amplification of c-MYC is a hallmark of a subset of poor-prognosis medulloblastoma. MYC upregulates glutamine metabolism across many types of cancer. We modified the naturally occurring glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) by adding 2 promoeities to increase its lipophilicity and brain penetration creating the prodrug isopropyl 6-diazo-5-oxo-2-(((phenyl (pivaloyloxy) methoxy) - carbonyl) amino) hexanoate, termed JHU395. This prodrug was shown to have a 10-fold improved CSF-to-plasma ratio and brain-to-plasma ratio relative to DON. We hypothesized that JHU395 would have superior cell penetration compared with DON and would effectively and more potently kill MYC-expressing medulloblastoma. JHU395 treatment caused decreased growth and increased apoptosis in multiple human high-MYC medulloblastoma cell lines at lower concentrations than DON. Parenteral administration of JHU395 in Nu/Nu mice led to the accumulation of micromolar concentrations of DON in brain. Treatment of mice bearing orthotopic xenografts of human MYC-amplified medulloblastoma with JHU395 increased median survival from 26 to 45 days compared with vehicle control mice (p &lt; 0.001 by log-rank test). These data provide preclinical justification for the ongoing development and testing of brain-targeted DON prodrugs for use in medulloblastoma.

scholarly journals Insights into the Action Mechanism of the Antimicrobial Peptide Lasioglossin III

2021 ◽  
Vol 22 (6) ◽  
pp. 2857
Author(s):  
Filomena Battista ◽  
Rosario Oliva ◽  
Pompea Del Vecchio ◽  
Roland Winter ◽  
Luigi Petraccone
Keyword(s):  
Antimicrobial Peptide ◽  
Gram Negative Bacteria ◽  
Lipid Domains ◽  
Action Mechanism ◽  
Cationic Antimicrobial Peptide ◽  
Intracellular Targeting ◽  
Gel Retardation Assay ◽  
Charged Membrane ◽  
Intracellular Target ◽  
Anionic Lipids

Lasioglossin III (LL-III) is a cationic antimicrobial peptide derived from the venom of the eusocial bee Lasioglossum laticeps. LL-III is extremely toxic to both Gram-positive and Gram-negative bacteria, and it exhibits antifungal as well as antitumor activity. Moreover, it shows low hemolytic activity, and it has almost no toxic effects on eukaryotic cells. However, the molecular basis of the LL-III mechanism of action is still unclear. In this study, we characterized by means of calorimetric (DSC) and spectroscopic (CD, fluorescence) techniques its interaction with liposomes composed of a mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-rac-phosphoglycerol (POPG) lipids as a model of the negatively charged membrane of pathogens. For comparison, the interaction of LL-III with the uncharged POPC liposomes was also studied. Our data showed that LL-III preferentially interacted with anionic lipids in the POPC/POPG liposomes and induces the formation of lipid domains. Furthermore, the leakage experiments showed that the peptide could permeabilize the membrane. Interestingly, our DSC results showed that the peptide-membrane interaction occurs in a non-disruptive manner, indicating an intracellular targeting mode of action for this peptide. Consistent with this hypothesis, our gel-retardation assay experiments showed that LL-III could interact with plasmid DNA, suggesting a possible intracellular target.

scholarly journals CELL PENETRATION BY ACIDS

1916 ◽  
Vol 24 (3) ◽  
pp. 255-279
Author(s):  
W.J. Crozier
Keyword(s):  
Cell Penetration
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