Emerging self-assembling peptide nanomaterial for anti-cancer therapy

2021 ◽  
pp. 088532822110278
Author(s):  
Lisheng Zhu ◽  
Yangyang Shi ◽  
Ying Xiong ◽  
Li Ba ◽  
Qiuting Li ◽  
...  
Keyword(s):  
Immune Escape ◽  
Vaccine Design ◽  
Resistant Cell ◽  
New Drugs ◽  
Multi Drug Resistance ◽  
Independent Manner ◽  
Self Assembling ◽  
Specific Proteins ◽  
Functional Peptide ◽  
Historical Transition

Recently it is mainly focused on anti-tumor comprehensive treatments like finding target tumor cells or activating immune cells to inhibit tumor recurrence and metastasis. At present, chemotherapy and molecular-targeted drugs can inhibit tumor cell growth to a certain extent. However, multi-drug resistance and immune escape often make it difficult for new drugs to achieve expected effects. Peptide hydrogel nanoparticles is a new type of biological material with functional peptide chains as the core and self-assembling peptide (SAP) as the framework. It has a variety of significant biological functions, including effective local inflammation suppression and non-drug-resistant cell killing. Besides, it can induce immune activation more persistently in an adjuvant independent manner when compared with simple peptides. Thus, SAP nanomaterial has great potential in regulating cell physiological functions, drug delivery and sensitization, vaccine design and immunotherapy. Not only that, it is also a potential way to focus on some specific proteins and cells through peptides, which has already been examined in previous research. A full understanding of the function and application of SAP nanoparticles can provide a simple and practical strategy for the development of anti-tumor drugs and vaccine design, which contributes to the historical transition of peptide nanohydrogels from bench to bedside and brings as much survival benefits as possible to cancer patients.

Combinatorial Peptide Libraries for Selecting Inorganic-Binding Proteins: A Step in Molecular Biomimetics

2003 ◽  
Vol 773 ◽  
Author(s):  
C. Tamerler ◽  
S. Dinçer ◽  
D. Heidel ◽  
N. Karagûler ◽  
M. Sarikaya
Keyword(s):  
Binding Proteins ◽  
Building Blocks ◽  
Molecular Engineering ◽  
Inorganic Materials ◽  
Combinatorial Peptide Libraries ◽  
Self Assembling ◽  
Complex Functions ◽  
Recent Developments ◽  
Specific Proteins ◽  
Molecular Biomimetics

AbstractProteins, one of the building blocks in organisms, not only control the assembly in biological systems but also provide most of their complex functions. It may be possible to assemble materials for practical technological applications utilizing the unique advantages provided by proteins. Here we discuss molecular biomimetic pathways in the quest for imitating biology at the molecular scale via protein engineering. We use combinatorial biology protocols to select short polypeptides that have affinity to inorganic materials and use them in assembling novel hybrid materials. We give an overview of some of the recent developments of molecular engineering towards this goal. Inorganic surface specific proteins were identified by using cell surface and phage display technologies. Examples of metal and metal oxide specific polypeptides were represented with an emphasis on certain level of specificities. The recognition and self assembling characteristics of these inorganic-binding proteins would be employed in develeopment of hybrid multifunctional materials for novel bio- and nano-technological applications.

scholarly journals Structural Basis for the Inhibition of RNase H Activity of HIV-1 Reverse Transcriptase by RNase H Active Site-Directed Inhibitors

2010 ◽  
Vol 84 (15) ◽  
pp. 7625-7633 ◽  
Author(s):  
Hua-Poo Su ◽  
Youwei Yan ◽  
G. Sridhar Prasad ◽  
Robert F. Smith ◽  
Christopher L. Daniels ◽  
...  
Keyword(s):  
Active Site ◽  
Thermal Denaturation ◽  
Binding Mode ◽  
Rnase H ◽  
New Drugs ◽  
Structural Basis ◽  
Independent Manner ◽  
Approved Drugs ◽  
Hiv 1 ◽  
Rapid Emergence

ABSTRACT HIV/AIDS continues to be a menace to public health. Several drugs currently on the market have successfully improved the ability to manage the viral burden in infected patients. However, new drugs are needed to combat the rapid emergence of mutated forms of the virus that are resistant to existing therapies. Currently, approved drugs target three of the four major enzyme activities encoded by the virus that are critical to the HIV life cycle. Although a number of inhibitors of HIV RNase H activity have been reported, few inhibit by directly engaging the RNase H active site. Here, we describe structures of naphthyridinone-containing inhibitors bound to the RNase H active site. This class of compounds binds to the active site via two metal ions that are coordinated by catalytic site residues, D443, E478, D498, and D549. The directionality of the naphthyridinone pharmacophore is restricted by the ordering of D549 and H539 in the RNase H domain. In addition, one of the naphthyridinone-based compounds was found to bind at a second site close to the polymerase active site and non-nucleoside/nucleotide inhibitor sites in a metal-independent manner. Further characterization, using fluorescence-based thermal denaturation and a crystal structure of the isolated RNase H domain reveals that this compound can also bind the RNase H site and retains the metal-dependent binding mode of this class of molecules. These structures provide a means for structurally guided design of novel RNase H inhibitors.

scholarly journals Functional Annotation and Curation of Hypothetical Proteins Present in A Newly Emerged Serotype 1c of Shigella flexneri: Emphasis on Selecting Targets for Virulence and Vaccine Design Studies

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 340
Author(s):  
Tanuka Sen ◽  
Naresh K. Verma
Keyword(s):  
Diarrheal Disease ◽  
Shigella Flexneri ◽  
Amino Acid Sequences ◽  
New Drugs ◽  
Homology Search ◽  
Multi Drug Resistance ◽  
Hypothetical Proteins ◽  
Signal Transducers ◽  
Bioinformatics Databases ◽  
Regulatory Functions

Shigella flexneri is the principal cause of bacillary dysentery, contributing significantly to the global burden of diarrheal disease. The appearance and increase in the multi-drug resistance among Shigella strains, necessitates further genetic studies and development of improved/new drugs against the pathogen. The presence of an abundance of hypothetical proteins in the genome and how little is known about them, make them interesting genetic targets. The present study aims to carry out characterization of the hypothetical proteins present in the genome of a newly emerged serotype of S. flexneri (strain Y394), toward their novel regulatory functions using various bioinformatics databases/tools. Analysis of the genome sequence rendered 4170 proteins, out of which 721 proteins were annotated as hypothetical proteins (HPs) with no known function. The amino acid sequences of these HPs were evaluated using a combination of latest bioinformatics tools based on homology search against functionally identified proteins. Functional domains were considered as the basis to infer the biological functions of HPs in this case and the annotation helped in assigning various classes to the proteins such as signal transducers, lipoproteins, enzymes, membrane proteins, transporters, virulence, and binding proteins. This study contributes to a better understanding of growth, survival, and disease mechanism at molecular level and provides potential new targets for designing drugs against Shigella infection.

Abstract 6541: Accounting for immune escape mechanisms in personalized and shared neoantigen cancer vaccine design

2020 ◽  
Author(s):  
Alexander Myronov ◽  
Iga Niemiec ◽  
Katarzyna Gruba ◽  
Giovanni Mazzocco ◽  
Anna Sanecka-Duin ◽  
...  
Keyword(s):  
Cancer Vaccine ◽  
Immune Escape ◽  
Vaccine Design ◽  
Immune Escape Mechanisms

scholarly journals Classification of self-assembling protein nanoparticle architectures for applications in vaccine design

2017 ◽  
Vol 4 (4) ◽  
pp. 161092 ◽  
Author(s):  
G. Indelicato ◽  
P. Burkhard ◽  
R. Twarock
Keyword(s):  
Self Assembly ◽  
Vaccine Design ◽  
Building Blocks ◽  
Coiled Coils ◽  
Specific Class ◽  
Regular Graphs ◽  
Humoral Immune ◽  
Self Assembling ◽  
Display Systems

We introduce here a mathematical procedure for the structural classification of a specific class of self-assembling protein nanoparticles (SAPNs) that are used as a platform for repetitive antigen display systems. These SAPNs have distinctive geometries as a consequence of the fact that their peptide building blocks are formed from two linked coiled coils that are designed to assemble into trimeric and pentameric clusters. This allows a mathematical description of particle architectures in terms of bipartite (3,5)-regular graphs. Exploiting the relation with fullerene graphs, we provide a complete atlas of SAPN morphologies. The classification enables a detailed understanding of the spectrum of possible particle geometries that can arise in the self-assembly process. Moreover, it provides a toolkit for a systematic exploitation of SAPNs in bioengineering in the context of vaccine design, predicting the density of B-cell epitopes on the SAPN surface, which is critical for a strong humoral immune response.

Immune Checkpoint Regulators: A New Era Toward Promising Cancer Therapy

2020 ◽  
Vol 20 (6) ◽  
pp. 429-460
Author(s):  
Mohammed Shaaban ◽  
Heba Othman ◽  
Takwa Ibrahim ◽  
Mariam Ali ◽  
Mohamed Abdelmoaty ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Immune Checkpoint ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Historical Background ◽  
New Era ◽  
Cancer Management ◽  
Immunosuppressive Tumor Microenvironment ◽  
Specific Proteins ◽  
Immune Editing

During the last century, our battle against cancer has been inaugurated upon three main approaches; surgery, radiation and chemotherapy. The latest findings on the effectiveness of immunotherapy in cancer management offer a ray of hope after decades of research and studies on the best treatment methods. Immunotherapy has proven effective in the surveillance and destruction of cancer- causing cells, demonstrating its ability to suppress cancer through controlling the wellestablished immune-editing process. Immuno-editing is a process that comprises three principal elements; elimination, equilibrium, and escape, and is paramount to the comprehension of checkpoint inhibition. Cancer cells employ various approaches to evade the elimination step leading to its immune- escape. The escape mechanism encompasses the up-regulation of negative co-signals that block successful activation of cancer-eradicating immune cells, developing cytokine background that favors the immunosuppressive tumor microenvironment (TME), or dropping the expression of tumor- specific proteins known as neo-antigens, therefore reducing the immunogenic activity against cancer cells. Today, checkpoint inhibitors are considered as a primary approach in our fight against cancer. Strategies targeting the inhibitory roles of checkpoint inhibitors have been shown effective against different cancer types and stages, and some already gained the FDA’s approval. This review seeks to comprehensively cover the historical background as well as the most recent updates for the role of immune checkpoint regulators in the maintenance of immune homeostatic balance as well as keeping the tumorigenic cells in check.

Extra-Pulmonary TB

2021 ◽  
pp. 91-116
Author(s):  
Sarita Rani ◽  
Ankur Kaul ◽  
Anil Kumar Mishra ◽  
Umesh Gupta
Keyword(s):  
Drug Resistance ◽  
Polymeric Micelles ◽  
New Drugs ◽  
Multi Drug Resistance ◽  
Liposomal Formulations ◽  
Extra Pulmonary ◽  
Stability Issues ◽  
Low Solubility ◽  
Line Drug ◽  
Extensively Drug Resistance

Tuberculosis is considered a fatal respiratory disease commonly seen in developing countries. This chapter includes the global scenario of TB patients and brief description of TB history, its pathogenesis, types, diagnosis tests, emergence of MDR (multi drug resistance) and XDR (extensively drug resistance). The traditional chemotherapy of TB includes first and second line drug therapy. These lines of therapies face many difficulties such as low solubility, low bioavailability, and stability issues. Therefore, some new drugs were introduced in the market that showed effective results to the patients. Nanoparticulate drug delivery gained much focus in recent years due to its advantages and ideal characteristics. Numerous nanoparticles, liposomal formulations, and polymeric micelles were reported by the researchers with significant and considerable results. Inhalable formulations were also prepared by scientists that showed effective and remarkable anti-tuberculosis action on TB patients. Many efforts are awaited to completely eradicate TB from the planet.

scholarly journals Glances in Immunology of HIV and HCV Infection

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Maria Giovanna Quaranta ◽  
Benedetta Mattioli ◽  
Stefano Vella
Keyword(s):  
Immune System ◽  
Immune Escape ◽  
Current Knowledge ◽  
Research Field ◽  
New Drugs ◽  
Host Immune System ◽  
Immune Recognition ◽  
Genetic Associations ◽  
Efficient Treatment ◽  
Adaptive Immune

Since the identification of HIV and HCV much progress has been made in the understanding of their life cycle and interaction with the host immune system. Despite these viruses markedly differ in their virological properties and in their pathogenesis, they share many common features in their immune escape and survival strategy. Both viruses have developed sophisticated ways to subvert and antagonize host innate and adaptive immune responses. In the last years, much effort has been done in the study of the AIDS pathogenesis and in the development of efficient treatment strategies, and a fatal infection has been transformed in a potentially chronic pathology. Much of this knowledge is now being transferred in the HCV research field, especially in the development of new drugs, although a big difference still remains between the outcome of the two infections, being HCV eradicable after treatment, whereas HIV eradication remains at present unachievable due to the establishment of reservoirs. In this review, we present current knowledge on innate and adaptive immune recognition and activation during HIV and HCV mono-infections and evasion strategies. We also discuss the genetic associations between components of the immune system, the course of infection, and the outcome of the therapies.

scholarly journals BCA2/Rabring7 Interferes with HIV-1 Proviral Transcription by Enhancing the SUMOylation of IκBα

2017 ◽  
Vol 91 (8) ◽  
Author(s):  
Marta Colomer-Lluch ◽  
Ruth Serra-Moreno
Keyword(s):  
New Drugs ◽  
Host Cells ◽  
Transcriptional Level ◽  
Lysosomal Degradation ◽  
Virus Propagation ◽  
Independent Manner ◽  
Virion Assembly ◽  
Sumo Ligase ◽  
Additional Barrier ◽  
Hiv 1

ABSTRACT BCA2/Rabring7 is a BST2 cofactor that promotes the lysosomal degradation of trapped HIV-1 virions but also functions as a BST2-independent anti-HIV factor by targeting Gag for lysosomal degradation. Since many antiviral factors regulate the NF-κB innate signaling pathway, we investigated whether BCA2 is also connected to this proinflammatory cascade. Here, we show for the first time that BCA2 is induced by NF-κB-activating proinflammatory cytokines and that upregulation of BCA2 provides regulatory negative feedback on NF-κB. Specifically, BCA2 serves as an E3 SUMO ligase in the SUMOylation of IκBα, which in turn enhances the sequestration of NF-κB components in the cytoplasm. Since HIV-1 utilizes NF-κB to promote proviral transcription, the BCA2-mediated inhibition of NF-κB significantly decreases the transcriptional activity of HIV-1 (up to 4.4-fold in CD4+ T cells). Therefore, our findings indicate that BCA2 poses an additional barrier to HIV-1 infection: not only does BCA2 prevent assembly and release of nascent virions, it also significantly restricts HIV-1 transcription by inhibiting the NF-κB pathway. IMPORTANCE Understanding the interactions between HIV-1 and its host cells is highly relevant to the design of new drugs aimed at eliminating HIV-1 from infected individuals. We have previously shown that BCA2, a cofactor of BST2 in the restriction of HIV-1, also prevents virion assembly in a BST2-independent manner. In this study, we found that BCA2 negatively regulates the NF-κB pathway—a signaling cascade necessary for HIV-1 replication and infectivity—which in turn detrimentally affects proviral transcription and virus propagation. Thus, our results indicate that, besides its previously described functions as an antiviral factor, BCA2 poses an additional barrier to HIV-1 replication at the transcriptional level.

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