scholarly journals Polyelectrolyte Encapsulation and Confinement within Protein Cage-Inspired Nanocompartments

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1551
Author(s):  
Qing Liu ◽  
Ahmed Shaukat ◽  
Daniella Kyllönen ◽  
Mauri A. Kostiainen
Keyword(s):  
Small Molecules ◽  
Driving Force ◽  
Electrostatic Interactions ◽  
Inorganic Nanoparticles ◽  
Wild Type ◽  
Potential Toxicity ◽  
Protein Cages ◽  
Functional Sites ◽  
Protein Cage ◽  
Or Gene

Protein cages are nanocompartments with a well-defined structure and monodisperse size. They are composed of several individual subunits and can be categorized as viral and non-viral protein cages. Native viral cages often exhibit a cationic interior, which binds the anionic nucleic acid genome through electrostatic interactions leading to efficient encapsulation. Non-viral cages can carry various cargo, ranging from small molecules to inorganic nanoparticles. Both cage types can be functionalized at targeted locations through genetic engineering or chemical modification to entrap materials through interactions that are inaccessible to wild-type cages. Moreover, the limited number of constitutional subunits ease the modification efforts, because a single modification on the subunit can lead to multiple functional sites on the cage surface. Increasing efforts have also been dedicated to the assembly of protein cage-mimicking structures or templated protein coatings. This review focuses on native and modified protein cages that have been used to encapsulate and package polyelectrolyte cargos and on the electrostatic interactions that are the driving force for the assembly of such structures. Selective encapsulation can protect the payload from the surroundings, shield the potential toxicity or even enhance the intended performance of the payload, which is appealing in drug or gene delivery and imaging.

scholarly journals Using the dendritic polymer PAMAM to form gold nanoparticles in the protein cage thermosome

2016 ◽  
Vol 52 (69) ◽  
pp. 10537-10539 ◽  
Author(s):  
Martin G. Nussbaumer ◽  
Christoph Bisig ◽  
Nico Bruns
Keyword(s):  
Gold Nanoparticles ◽  
Metal Ions ◽  
Inorganic Nanoparticles ◽  
Dendritic Polymer ◽  
Protein Cages ◽  
Protein Cage

Many protein cages, including the chaperonin thermosome (THS), lack the ability to form inorganic nanoparticles. By conjugation of PAMAM into THS, metal ions could bind to the dendrimer and allowed the formation of gold nanoparticles in the protein cage.

Synthesis of Metal Core in the Apoferritin Cavity

2012 ◽  
Vol 549 ◽  
pp. 216-220
Author(s):  
Ting Wang
Keyword(s):  
Particle Size ◽  
Electrostatic Interactions ◽  
Molecular Level ◽  
Reaction Vessel ◽  
Inorganic Materials ◽  
Metal Core ◽  
Protein Cages ◽  
Protein Cage ◽  
Protein Cavity ◽  
Uniform Particle Size

Many methods to produce NPs have been studied. Among them, the molecular level understanding of the formation of solids in biological systems has provided inspiration for the controlled formation of novel inorganic materials. The use of a protein cavity as the growth field of NPs provides one candidate method for obtaining uniform particle size. The host-guest relationship between these protein cages and the encapsulated material is based primarily on a complementary electrostatic interaction. Charged interfaces play important roles in defining electrostatically distinct environments for spatially defined encapsulation. The electrostatic interactions can be approximated by Guoy-Chapman theory of charged interfaces. These interactions are proposed at the interior of protein cages such as ferritin and viruses. The protein cage with a highly charged interior surface with pores that allow molecular access to the inside of the protein could act as a constrained reaction vessel. The present paper will focus on the synthesis of Metal NPs using ferritin.

scholarly journals In vitro-reassembled plant virus-like particles for loading of polyacids

2006 ◽  
Vol 87 (9) ◽  
pp. 2749-2754 ◽  
Author(s):  
Yupeng Ren ◽  
Sek-Man Wong ◽  
Lee-Yong Lim
Keyword(s):  
Electrostatic Interactions ◽  
Plant Viruses ◽  
Virus Like Particles ◽  
Protein Cages ◽  
Large Molecules ◽  
Protein Cage ◽  
Drug Molecules ◽  
Structural Conformation ◽  
Foreign Materials

The coat protein (CP) of certain plant viruses may reassemble into empty virus-like particles (VLPs) and these protein cages may serve as potential drug delivery platforms. In this paper, the production of novel VLPs from the Hibiscus chlorotic ringspot virus (HCRSV) is reported and the capacity to load foreign materials was characterized. VLPs were readily produced by destabilizing the HCRSV in 8 M urea or Tris buffer pH 8, in the absence of calcium ions, followed by removal of viral RNA by ultrahigh-speed centrifugation and the reassembly of the CP in sodium acetate buffer pH 5. The loading of foreign materials into the VLPs was dependent on electrostatic interactions. Anionic polyacids, such as polystyrenesulfonic acid and polyacrylic acid, were successfully loaded but neutrally charged dextran molecules were not. The molecular-mass threshold for the polyacid cargo was about 13 kDa, due to the poor retention of smaller molecules, which readily diffused through the holes between the S domains present on the surface of the VLPs. These holes precluded the entry of large molecules, but allowed smaller molecules to enter or exit. The polyacid-loaded VLPs had comparable size, morphology and surface-charge density to the native HCRSV, and the amount of polyacids loaded was comparable to the weight of the native genomic materials. The conditions applied to disassembly–reassembly of the virions did not change the structural conformation of the CP. HCRSV-derived VLPs may provide a promising nano-sized protein cage for delivery of anionic drug molecules.

scholarly journals Relative importance of driving force and electrostatic interactions in the reduction of multihaem cytochromes by small molecules

2013 ◽  
Vol 1827 (6) ◽  
pp. 745-750 ◽  
Author(s):  
Pedro O. Quintas ◽  
Andreia P. Cepeda ◽  
Nuno Borges ◽  
Teresa Catarino ◽  
David L. Turner
Keyword(s):  
Small Molecules ◽  
Driving Force ◽  
Electrostatic Interactions ◽  
Relative Importance

Systematic Engineering of a Protein Nanocage for High-Yield, Site-Specific Modification

2018 ◽  
Author(s):  
Daniel D. Brauer ◽  
Emily C. Hartman ◽  
Daniel L.V. Bader ◽  
Zoe N. Merz ◽  
Danielle Tullman-Ercek ◽  
...  
Keyword(s):  
Small Molecules ◽  
Protein Modification ◽  
Positive Charge ◽  
Specific Protein ◽  
High Yield ◽  
Site Specific ◽  
Protein Cage ◽  
Protein Carriers ◽  
Site Selective ◽  
Targeted Library

<div> <p>Site-specific protein modification is a widely-used strategy to attach drugs, imaging agents, or other useful small molecules to protein carriers. N-terminal modification is particularly useful as a high-yielding, site-selective modification strategy that can be compatible with a wide array of proteins. However, this modification strategy is incompatible with proteins with buried or sterically-hindered N termini, such as virus-like particles like the well-studied MS2 bacteriophage coat protein. To assess VLPs with improved compatibility with these techniques, we generated a targeted library based on the MS2-derived protein cage with N-terminal proline residues followed by three variable positions. We subjected the library to assembly, heat, and chemical selections, and we identified variants that were modified in high yield with no reduction in thermostability. Positive charge adjacent to the native N terminus is surprisingly beneficial for successful extension, and over 50% of the highest performing variants contained positive charge at this position. Taken together, these studies described nonintuitive design rules governing N-terminal extensions and identified successful extensions with high modification potential.</p> </div>

scholarly journals Factors Conditioning the Potential Effects TiO2 NPs Exposure on Human Microbiota: a Mini-Review

2021 ◽  
Author(s):  
Ewa Baranowska-Wójcik
Keyword(s):  
Titanium Dioxide Nanoparticles ◽  
Intestinal Barrier ◽  
Inorganic Nanoparticles ◽  
Potential Toxicity ◽  
Human Microbiota ◽  
Significant Interest ◽  
Inflammatory Bowel ◽  
Wide Group ◽  
The Impact ◽  
White Colour

AbstractThe recent years have seen a significant interest in the applications of nanotechnology in various facets of our lives. Due to their increasingly widespread use, human exposure to nanoparticles (NPs) is fast becoming unavoidable. Among the wide group of nanoparticles currently employed in industry, titanium dioxide nanoparticles, TiO2 NPs, are particularly popular. Due to its white colour, TiO2 is widely used as a whitening food additive (E 171). Yet, there have been few studies aimed at determining its direct impact on bacteria, while the available data suggest that TiO2 NPs may influence microbiota causing problems such as inflammatory bowel disease, obesity, or immunological disorders. Indeed, there are increasing concerns that its presence may lead to intestinal barrier impairment, including dysbiosis of intestinal microbiota. This article aims to present an overview of studies conducted to date with regard to the impact of TiO2 NPs on human microbiota as well as factors that can affect the same. Such information is necessary if we are to conclusively determine the potential toxicity of inorganic nanoparticles.

The Budding Yeast Msh4 Protein Functions in Chromosome Synapsis and the Regulation of Crossover Distribution

Genetics ◽  
2001 ◽  
Vol 158 (3) ◽  
pp. 1013-1025 ◽  
Author(s):  
Janet E Novak ◽  
Petra B Ross-Macdonald ◽  
G Shirleen Roeder
Keyword(s):  
Mismatch Repair ◽  
Budding Yeast ◽  
Null Mutation ◽  
Crossing Over ◽  
Wild Type ◽  
Crossover Interference ◽  
Meiotic Chromosomes ◽  
Chromosome Synapsis ◽  
Protein Functions ◽  
Or Gene

AbstractThe budding yeast MSH4 gene encodes a MutS homolog produced specifically in meiotic cells. Msh4 is not required for meiotic mismatch repair or gene conversion, but it is required for wild-type levels of crossing over. Here, we show that a msh4 null mutation substantially decreases crossover interference. With respect to the defect in interference and the level of crossing over, msh4 is similar to the zip1 mutant, which lacks a structural component of the synaptonemal complex (SC). Furthermore, epistasis tests indicate that msh4 and zip1 affect the same subset of meiotic crossovers. In the msh4 mutant, SC formation is delayed compared to wild type, and full synapsis is achieved in only about half of all nuclei. The simultaneous defects in synapsis and interference observed in msh4 (and also zip1 and ndj1/tam1) suggest a role for the SC in mediating interference. The Msh4 protein localizes to discrete foci on meiotic chromosomes and colocalizes with Zip2, a protein involved in the initiation of chromosome synapsis. Both Zip2 and Zip1 are required for the normal localization of Msh4 to chromosomes, raising the possibility that the zip1 and zip2 defects in crossing over are indirect, resulting from the failure to localize Msh4 properly.

scholarly journals Structural and Drug Targeting Insights on Mutant p53

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3344
Author(s):  
Ana Sara Gomes ◽  
Helena Ramos ◽  
Alberto Inga ◽  
Emília Sousa ◽  
Lucília Saraiva
Keyword(s):  
Small Molecules ◽  
Drug Targeting ◽  
Normal Function ◽  
Structure Stability ◽  
Mutant P53 ◽  
Structural Studies ◽  
Wild Type ◽  
Tumor Onset ◽  
Long Time ◽  
Stability Dynamics

p53 is a transcription factor with a pivotal role in cell homeostasis and fate. Its impairment is a major event in tumor onset and development. In fact, about half of human cancers bear TP53 mutations that not only halt the normal function of p53, but also may acquire oncogenic gain of functions that favor tumorigenesis. Although considered undruggable for a long time, evidence has proven the capability of many compounds to restore a wild-type (wt)-like function to mutant p53 (mutp53). However, they have not reached the clinic to date. Structural studies have strongly contributed to the knowledge about p53 structure, stability, dynamics, function, and regulation. Importantly, they have afforded relevant insights into wt and mutp53 pharmacology at molecular levels, fostering the design and development of p53-targeted anticancer therapies. Herein, we provide an integrated view of mutp53 regulation, particularly focusing on mutp53 structural traits and on targeting agents capable of its reactivation, including their biological, biochemical and biophysical features. With this, we expect to pave the way for the development of improved small molecules that may advance precision cancer therapy by targeting p53.

scholarly journals Semi-Synthesis of Small Molecules of Aminocarbazoles: Tumor Growth Inhibition and Potential Impact on p53

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1637
Author(s):  
Solida Long ◽  
Joana B. Loureiro ◽  
Carla Carvalho ◽  
Luís Gales ◽  
Lucília Saraiva ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Small Molecules ◽  
Tumor Cells ◽  
Mutant P53 ◽  
Wild Type ◽  
Naturally Occurring ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Amino Derivatives ◽  
Carbazole Alkaloids

The tumor suppressor p53 is inactivated by mutation in approximately 50% of human cancers. Small molecules that bind and stabilize those mutants may represent effective anticancer drugs. Herein, we report the tumor cell growth inhibitory activity of carbazole alkaloids and amino derivatives, as well as their potential activation of p53. Twelve aminocarbazole alkaloids were semi-synthesized from heptaphylline (1), 7-methoxy heptaphylline (2), and 7-methoxymukonal (3), isolated from Clausena harmandiana, using a reductive amination protocol. Naturally-occurring carbazoles 1–3 and their amino derivatives were evaluated for their potential effect on wild-type and mutant p53 activity using a yeast screening assay and on human tumor cell lines. Naturally-occurring carbazoles 1–3 showed the most potent growth inhibitory effects on wild-type p53-expressing cells, being heptaphylline (1) the most promising in all the investigated cell lines. However, compound 1 also showed growth inhibition against non-tumor cells. Conversely, semi-synthetic aminocarbazole 1d showed an interesting growth inhibitory activity in tumor cells expressing both wild-type and mutant p53, exhibiting low growth inhibition on non-tumor cells. The yeast assay showed a potential reactivation of mutant p53 by heptaphylline derivatives, including compound 1d. The results obtained indicate that carbazole alkaloids may represent a promising starting point to search for new mutp53-reactivating agents with promising applications in cancer therapy.

scholarly journals TERT promoter hotspot mutations and gene amplification in metaplastic breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Edaise M. da Silva ◽  
Pier Selenica ◽  
Mahsa Vahdatinia ◽  
Fresia Pareja ◽  
Arnaud Da Cruz Paula ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Amplification ◽  
Genetic Alterations ◽  
Wild Type ◽  
Histologic Subtype ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Fisher’S Exact Test ◽  
Hotspot Mutations ◽  
Or Gene

AbstractMetaplastic breast cancers (MBCs) are characterized by complex genomes, which seem to vary according to their histologic subtype. TERT promoter hotspot mutations and gene amplification are rare in common forms of breast cancer, but present in a subset of phyllodes tumors. Here, we sought to determine the frequency of genetic alterations affecting TERT in a cohort of 60 MBCs with distinct predominant metaplastic components (squamous, 23%; spindle, 27%; osseous, 8%; chondroid, 42%), and to compare the repertoire of genetic alterations of MBCs according to the presence of TERT promoter hotspot mutations or gene amplification. Forty-four MBCs were subjected to: whole-exome sequencing (WES; n = 27) or targeted sequencing of 341-468 cancer-related genes (n = 17); 16 MBCs were subjected to Sanger sequencing of the TERT promoter, TP53 and selected exons of PIK3CA, HRAS, and BRAF. TERT promoter hotspot mutations (n = 9) and TERT gene amplification (n = 1) were found in 10 of the 60 MBCs analyzed, respectively. These TERT alterations were less frequently found in MBCs with predominant chondroid differentiation than in other MBC subtypes (p = 0.01, Fisher’s exact test) and were mutually exclusive with TP53 mutations (p < 0.001, CoMEt). In addition, a comparative analysis of the MBCs subjected to WES or targeted cancer gene sequencing (n = 44) revealed that MBCs harboring TERT promoter hotspot mutations or gene amplification (n = 6) more frequently harbored PIK3CA than TERT wild-type MBCs (n = 38; p = 0.001; Fisher’s exact test). In conclusion, TERT somatic genetic alterations are found in a subset of TP53 wild-type MBCs with squamous/spindle differentiation, highlighting the genetic diversity of these cancers.

Sign in / Sign up

Export Citation Format

Share Document