scholarly journals StreptomeDB 3.0: an updated compendium of streptomycetes natural products

2020 ◽  
Vol 49 (D1) ◽  
pp. D600-D604 ◽  
Author(s):  
Aurélien F A Moumbock ◽  
Mingjie Gao ◽  
Ammar Qaseem ◽  
Jianyu Li ◽  
Pascal A Kirchner ◽  
...  
Keyword(s):  
Natural Products ◽  
Rational Design ◽  
Rapid Development ◽  
Life Sciences ◽  
Online Database ◽  
Genus Streptomyces ◽  
Manual Curation ◽  
A Genome ◽  
Data Content ◽  
Prediction Server

Abstract Antimicrobial resistance is an emerging global health threat necessitating the rapid development of novel antimicrobials. Remarkably, the vast majority of currently available antibiotics are natural products (NPs) isolated from streptomycetes, soil-dwelling bacteria of the genus Streptomyces. However, there is still a huge reservoir of streptomycetes NPs which remains pharmaceutically untapped and a compendium thereof could serve as a source of inspiration for the rational design of novel antibiotics. Initially released in 2012, StreptomeDB (http://www.pharmbioinf.uni-freiburg.de/streptomedb) is the first and only public online database that enables the interactive phylogenetic exploration of streptomycetes and their isolated or mutasynthesized NPs. In this third release, there are substantial improvements over its forerunners, especially in terms of data content. For instance, about 2500 unique NPs were newly annotated through manual curation of about 1300 PubMed-indexed articles, published in the last five years since the second release. To increase interoperability, StreptomeDB entries were hyperlinked to several spectral, (bio)chemical and chemical vendor databases, and also to a genome-based NP prediction server. Moreover, predicted pharmacokinetic and toxicity profiles were added. Lastly, some recent real-world use cases of StreptomeDB are highlighted, to illustrate its applicability in life sciences.

Natural Products for the Treatment of Neurodegenerative Diseases

2020 ◽  
Vol 27 (34) ◽  
pp. 5790-5828 ◽  
Author(s):  
Ze Wang ◽  
Chunyang He ◽  
Jing-Shan Shi
Keyword(s):  
Nervous System ◽  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Neuroprotective Effect ◽  
Rapid Development ◽  
New Drugs ◽  
Progressive Degeneration ◽  
Cord Injury ◽  
The Central Nervous System ◽  
And Function

Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. Alzheimer's Disease (AD), Parkinson's Disease (PD) and Spinal Cord Injury (SCI) are the common neurodegenerative diseases, which typically occur in people over the age of 60. With the rapid development of an aged society, over 60 million people worldwide are suffering from these uncurable diseases. Therefore, the search for new drugs and therapeutic methods has become an increasingly important research topic. Natural products especially those from the Traditional Chinese Medicines (TCMs), are the most important sources of drugs, and have received extensive interest among pharmacist. In this review, in order to facilitate further chemical modification of those useful natural products by pharmacists, we will bring together recent studies in single natural compound from TCMs with neuroprotective effect.

Cancer Proteomics: New Horizons and Insights into Therapeutic Applications

2020 ◽  
Vol 17 ◽  
Author(s):  
Perumal Subramaniana ◽  
Jaime Jacqueline Jayapalan ◽  
Puteri Shafinaz Abdul-Rahmanb
Keyword(s):  
Molecular Mechanisms ◽  
Rapid Development ◽  
New Horizons ◽  
Cancer Management ◽  
Proteomic Approach ◽  
Cancer Proteomics ◽  
Therapeutic Outcomes ◽  
A Genome ◽  
Highly Sensitive ◽  
Dimensional Electrophoresis

A proteome is an efficient rendition of a genome, unswervingly controlling various cancer processes. Molecular mechanisms of several cancer processes have been unraveled by proteomic approach. Thus far, numerous tumors of diverse status have been investigated by two-dimensional electrophoresis. Numerous biomarkers have been recognized and precise categorization of apparent lesions has led to the timely detection of various cancers in persons at peril. Currently used pioneering approaches and technologies in proteomics have led to highly sensitive assays of cancer biomarkers and improved the early diagnosis of various cancers. The discovery of novel and definite biomarker signatures further widened our perceptive of the disease and novel potent drugs for efficient and aimed therapeutic outcomes in persistent cancers have emerged. However, a major limitation, even today, of proteomics is resolving and quantifying the proteins of low abundance. Despite the rapid development of proteomic technologies and their applications in cancer management, annulling the shortcomings of present proteomic technologies and development of better methods are still desirable. The main objectives of this review are to discuss the developing aspects, merits and demerits of pharmacoproteomics, redox proteomics, novel approaches and therapies being used for various types of cancer based on proteome studies.

Rational design of MnCo2O4@NC@MnO2 three-layered core–shell octahedron for high-rate and long-life lithium storage

2018 ◽  
Vol 47 (41) ◽  
pp. 14540-14548 ◽  
Author(s):  
Peng Huang ◽  
Ming Zhao ◽  
Bo Jin ◽  
Huan Li ◽  
Zhi Zhu ◽  
...  
Keyword(s):  
Energy Demand ◽  
Rational Design ◽  
Rapid Development ◽  
Lithium Ion ◽  
High Rate ◽  
Core Shell ◽  
Lithium Storage ◽  
Fossil Energy ◽  
Long Life ◽  
Current Energy

With the depletion of fossil energy and rapid development of electronic equipment, the commercial lithium-ion batteries (LIBs) do not meet the current energy demand.

scholarly journals Excited state dynamics for visible-light sensitization of a photochromic benzil-subsituted phenoxyl-imidazolyl radical

2019 ◽  
Vol 15 ◽  
pp. 2369-2379
Author(s):  
Yoichi Kobayashi ◽  
Yukie Mamiya ◽  
Katsuya Mutoh ◽  
Hikaru Sotome ◽  
Masafumi Koga ◽  
...  
Keyword(s):  
Visible Light ◽  
Rational Design ◽  
Materials Science ◽  
Transient Absorption ◽  
Life Sciences ◽  
Transient Absorption Spectroscopy ◽  
Back Reaction ◽  
Switching Speed ◽  
Wide Range ◽  
Potential Applications

Visible-light sensitized photoswitches have been paid particular attention in the fields of life sciences and materials science because long-wavelength light reduces photodegradation, transmits deep inside of matters, and achieves the selective excitation in condensed systems. Among various photoswitch molecules, the phenoxyl-imidazolyl radical complex (PIC) is a recently developed thermally reversible photochromic molecule whose thermal back reaction can be tuned from tens of nanoseconds to tens of seconds by rational design of the molecular structure. While the wide range of tunability of the switching speed of PIC opened up various potential applications, no photosensitivity to visible light limits its applications. In this study, we synthesized a visible-light sensitized PIC derivative conjugated with a benzil unit. Femtosecond transient absorption spectroscopy revealed that the benzil unit acts as a singlet photosensitizer for PIC by the Dexter-type energy transfer. Visible-light sensitized photochromic reactions of PIC are important for expanding the versatility of potential applications to life sciences and materials science.

scholarly journals Pathogenic Viruses Commonly Present in the Oral Cavity and Relevant Antiviral Compounds Derived from Natural Products

Medicines ◽  
2018 ◽  
Vol 5 (4) ◽  
pp. 120 ◽  
Author(s):  
Daisuke Asai ◽  
Hideki Nakashima
Keyword(s):  
Natural Products ◽  
Oral Cavity ◽  
Rational Design ◽  
Large Scale ◽  
Antiviral Agents ◽  
Marine Sponges ◽  
Design Strategies ◽  
Screening Programs ◽  
Human Oral Cavity ◽  
Antiviral Compounds

Many viruses, such as human herpesviruses, may be present in the human oral cavity, but most are usually asymptomatic. However, if individuals become immunocompromised by age, illness, or as a side effect of therapy, these dormant viruses can be activated and produce a variety of pathological changes in the oral mucosa. Unfortunately, available treatments for viral infectious diseases are limited, because (1) there are diseases for which no treatment is available; (2) drug-resistant strains of virus may appear; (3) incomplete eradication of virus may lead to recurrence. Rational design strategies are widely used to optimize the potency and selectivity of drug candidates, but discovery of leads for new antiviral agents, especially leads with novel structures, still relies mostly on large-scale screening programs, and many hits are found among natural products, such as extracts of marine sponges, sea algae, plants, and arthropods. Here, we review representative viruses found in the human oral cavity and their effects, together with relevant antiviral compounds derived from natural products. We also highlight some recent emerging pharmaceutical technologies with potential to deliver antivirals more effectively for disease prevention and therapy.

scholarly journals RNA Secondary Structure as a First Step for Rational Design of the Oligonucleotides towards Inhibition of Influenza A Virus Replication

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 925 ◽  
Author(s):  
Marta Szabat ◽  
Dagny Lorent ◽  
Tomasz Czapik ◽  
Maria Tomaszewska ◽  
Elzbieta Kierzek ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Influenza A Virus ◽  
Influenza A ◽  
Rational Design ◽  
Rna Virus ◽  
Viral Rna ◽  
Structure Information ◽  
A Genome ◽  
Function Relationship ◽  
Interfering Rna

Influenza is an important research subject around the world because of its threat to humanity. Influenza A virus (IAV) causes seasonal epidemics and sporadic, but dangerous pandemics. A rapid antigen changes and recombination of the viral RNA genome contribute to the reduced effectiveness of vaccination and anti-influenza drugs. Hence, there is a necessity to develop new antiviral drugs and strategies to limit the influenza spread. IAV is a single-stranded negative sense RNA virus with a genome (viral RNA—vRNA) consisting of eight segments. Segments within influenza virion are assembled into viral ribonucleoprotein (vRNP) complexes that are independent transcription-replication units. Each step in the influenza life cycle is regulated by the RNA and is dependent on its interplay and dynamics. Therefore, viral RNA can be a proper target to design novel therapeutics. Here, we briefly described examples of anti-influenza strategies based on the antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA (miRNA) and catalytic nucleic acids. In particular we focused on the vRNA structure-function relationship as well as presented the advantages of using secondary structure information in predicting therapeutic targets and the potential future of this field.

scholarly journals Marine natural products

2015 ◽  
Vol 32 (2) ◽  
pp. 116-211 ◽  
Author(s):  
John W. Blunt ◽  
Brent R. Copp ◽  
Robert A. Keyzers ◽  
Murray H. G. Munro ◽  
Michèle R. Prinsep
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Phase I ◽  
Marine Natural Products ◽  
Rapid Development ◽  
Phase I Clinical Trials ◽  
New Compounds

This review of marine natural products for 2013 describes 1137 new compounds and reports structural revisions and assignments of absolute configurations for previously described compounds. Included is a report of the anticancer sponge metabolite PM060184 that has undergone a remarkably rapid development from discovery in 2005 to the commencement of phase I clinical trials in 2011.

scholarly journals Multicomponent gold nano-glycoconjugate as a highly immunogenic and protective platform against Burkholderia mallei

npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Daniel Tapia ◽  
Javier I. Sanchez-Villamil ◽  
Alfredo G. Torres
Keyword(s):  
Rational Design ◽  
Antibody Responses ◽  
Effective Vaccine ◽  
Antigen Delivery ◽  
Burkholderia Mallei ◽  
Protein Antigens ◽  
Intrinsic Resistance ◽  
Vaccine Platform ◽  
A Genome

Abstract Burkholderia mallei (Bm) is a facultative intracellular pathogen and the etiological agent of glanders, a highly infectious zoonotic disease occurring in equines and humans. The intrinsic resistance to antibiotics, lack of specific therapy, high mortality, and history as a biothreat agent, prompt the need of a safe and effective vaccine. However, the limited knowledge of protective Bm-specific antigens has hampered the development of a vaccine. Further, the use of antigen-delivery systems that enhance antigen immunogenicity and elicit robust antigen-specific immune responses has been limited and could improve vaccines against Bm. Nanovaccines, in particular gold nanoparticles (AuNPs), have been investigated as a strategy to broaden the repertoire of vaccine-mediated immunity and as a tool to produce multivalent vaccines. To synthesize a nano-glycoconjugate vaccine, six predicted highly immunogenic antigens identified by a genome-wide bio- and immuno-informatic analysis were purified and coupled to AuNPs along with lipopolysaccharide (LPS) from B. thailandensis. Mice immunized intranasally with individual AuNP-protein-LPS conjugates, showed variable degrees of protection against intranasal Bm infection, while an optimized combination formulation (containing protein antigens OmpW, OpcP, and Hemagglutinin, along with LPS) showed complete protection against lethality in a mouse model of inhalational glanders. Animals immunized with different nano-glycoconjugates showed robust antigen-specific antibody responses. Moreover, serum from animals immunized with the optimized nano-glycoconjugate formulation showed sustained antibody responses with increased serum-mediated inhibition of adherence and opsonophagocytic activity in vitro. This study provides the basis for the rational design and construction of a multicomponent vaccine platform against Bm.

Genome-wide screening antifungal genes in Streptomyces griseus S4-7, a Fusarium wilt disease suppressive microbial agent

2019 ◽  
Vol 366 (12) ◽  
Author(s):  
Sung Won Hong ◽  
Da-Ran Kim ◽  
Youn Sang Kwon ◽  
Youn-Sig Kwak
Keyword(s):  
Antifungal Activity ◽  
Secondary Metabolites ◽  
Fusarium Wilt ◽  
Streptomyces Griseus ◽  
Wilt Disease ◽  
Inverse Pcr ◽  
Genus Streptomyces ◽  
Fusarium Wilt Disease ◽  
Genome Wide ◽  
A Genome

ABSTRACT Streptomyces is a widely studied bacterial genus, particularly with regard to secondary metabolites and antibiotics production. Streptomyces griseus S4–7 was isolated from a strawberry Fusarium wilt disease suppressive soil, and its biological control ability has been well established. However, the antifungal mechanism of strain S4–7 is not yet fully understood at the molecular and biochemical level. Therefore, in this study we created a random mutant library for strain S4–7 with the Tn5 transposon element to investigate antifungal traits on a genome-wide scale. In total 4646 individual mutant strains were created and 13 mutants were selected based on loss of antifungal activity. The knockout genes were identified as electron transfer oxidoreductase (eto),sigma factor-70(sig70) and nrps by Inverse PCR (I-PCR). eto regulates the geranylgeranyl reductase gene, which is involved in terpenoid-quinone biosynthesis, an important factor in cell fitness. In the △eto strain, expression of wbl, a master regulator of the production of secondary metabolites, was significantly reduced. sig70 is responsible for the cell differentiation sensing mechanism in genus Streptomyces. △nrps showed decreased production of hybrid peptide-polyketide siderophores. These results suggest that S. griseus S4–7 may have various antifungal mechanisms, and each mechanism is essential to maximal antifungal activity.

Mechanical Features of Cable-Girder Anchorage for Long-Span Railway Cable-Stayed Bridge with Steel Box Girders

2014 ◽  
Vol 587-589 ◽  
pp. 1391-1394 ◽  
Author(s):  
Chao Yi Yao ◽  
Qian Hui Pu ◽  
Ya Dong Yao
Keyword(s):  
Stress Distribution ◽  
Rational Design ◽  
Load Transfer ◽  
Rapid Development ◽  
Transfer Mechanism ◽  
Complex Load ◽  
Cable Stayed Bridge ◽  
Long Span ◽  
Load Transfer Mechanism ◽  
Cable Stayed Bridges

The cable-stayed bridge got rapid development in recent years. And for long-span cable-stayed bridges, the cable-girder anchorage structure is a key component in designing. The function of the cable-girder anchorage structure is to transfer the load between cables and the main girder. With the complex load transfer mechanism and stress concentration induced by large cable force, rational design of cable-girder anchorage structure is critical to long-span cable-stayed bridges. Take a certain long-span railway cable-stayed bridge in Zhejiang Province as the investigation, the load transfer mechanism and the stress distribution state was studied by finite element model. The research indicated that the design of this anchor box was rational. The stress distribution on each plate of the anchor box was relatively uniform. And the load transfer path and mechanisms of the main components of this anchor box were clear.

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