scholarly journals Description and analysis of glycosidic residues in the largest open natural products database

2021 ◽  
Author(s):  
Jonas Schaub ◽  
Achim Zielesny ◽  
Christoph Steinbeck ◽  
Maria Sorokina
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Pharmaceutical Industry ◽  
Receptor Binding ◽  
Structural Characteristics ◽  
Molecular Transport ◽  
Target Specificity ◽  
Starting Point ◽  
Living Organisms

AbstractNatural products (NP), biomolecules produced by living organisms, inspire the pharmaceutical industry and research due to their structural characteristics and the substituents from which they derive their activities. Glycosidic residues are frequently present in NP structures and have particular pharmacokinetic and pharmacodynamic importance as they improve their solubility and are often involved in molecular transport, target specificity, ligand-target interactions and receptor binding. The COlleCtion of Open Natural prodUcTs (COCONUT) is currently the largest open database of NP and therefore a suitable starting point for the detection and analysis of the diversity of glycosidic residues in NP. In this work, we report and describe the presence of circular, linear, terminal and non-terminal glycosidic units in NP, together with their importance in drug discovery.

scholarly journals Description and Analysis of Glycosidic Residues in the Largest Open Natural Products Database

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 486
Author(s):  
Jonas Schaub ◽  
Achim Zielesny ◽  
Christoph Steinbeck ◽  
Maria Sorokina
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Pharmaceutical Industry ◽  
Receptor Binding ◽  
Structural Characteristics ◽  
Molecular Transport ◽  
Target Specificity ◽  
Starting Point ◽  
Living Organisms

Natural products (NPs), biomolecules produced by living organisms, inspire the pharmaceutical industry and research due to their structural characteristics and the substituents from which they derive their activities. Glycosidic residues are frequently present in NP structures and have particular pharmacokinetic and pharmacodynamic importance as they improve their solubility and are often involved in molecular transport, target specificity, ligand–target interactions, and receptor binding. The COlleCtion of Open Natural prodUcTs (COCONUT) is currently the largest open database of NPs, and therefore a suitable starting point for the detection and analysis of the diversity of glycosidic residues in NPs. In this work, we report and describe the presence of circular, linear, terminal, and non-terminal glycosidic units in NPs, together with their importance in drug discovery.

scholarly journals Natural Products as Modulators of Sirtuins

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3287 ◽  
Author(s):  
Berin Karaman Mayack ◽  
Wolfgang Sippl ◽  
Fidele Ntie-Kang
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Histone Deacetylases ◽  
High Throughput Screening ◽  
Chemical Space ◽  
Class Iii ◽  
Drug Candidates ◽  
Starting Point ◽  
Recent Developments ◽  
Potent Drug

Natural products have been used for the treatment of human diseases since ancient history. Over time, due to the lack of precise tools and techniques for the separation, purification, and structural elucidation of active constituents in natural resources there has been a decline in financial support and efforts in characterization of natural products. Advances in the design of chemical compounds and the understanding of their functions is of pharmacological importance for the biomedical field. However, natural products regained attention as sources of novel drug candidates upon recent developments and progress in technology. Natural compounds were shown to bear an inherent ability to bind to biomacromolecules and cover an unparalleled chemical space in comparison to most libraries used for high-throughput screening. Thus, natural products hold a great potential for the drug discovery of new scaffolds for therapeutic targets such as sirtuins. Sirtuins are Class III histone deacetylases that have been linked to many diseases such as Parkinson`s disease, Alzheimer’s disease, type II diabetes, and cancer linked to aging. In this review, we examine the revitalization of interest in natural products for drug discovery and discuss natural product modulators of sirtuins that could serve as a starting point for the development of isoform selective and highly potent drug-like compounds, as well as the potential application of naturally occurring sirtuin inhibitors in human health and those in clinical trials.

scholarly journals Genomics-directed activation of cryptic natural product pathways deciphers codes for biosynthesis and molecular function

2020 ◽  
Author(s):  
Yuta Tsunematsu
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Expression System ◽  
Regulatory Gene ◽  
Efficient Production ◽  
Molecular Function ◽  
Biosynthetic Genes ◽  
Ancient Times ◽  
Living Organisms ◽  
Enzyme Functions

AbstractNatural products, which can be isolated from living organisms worldwide, have played a pivotal role in drug discovery since ancient times. However, it has become more challenging to identify a structurally novel molecule with promising biological activity for pharmaceutical development, mainly due to the limited methodologies for their acquisition. In this review, we summarize our recent studies that activate the biosynthetic potential of filamentous fungi by genetic engineering to harness the metabolic flow for the efficient production of unprecedented natural products. The recent revolution in genome sequencing technology enables the accumulation of vast amounts of information on biosynthetic genes, the blueprint of the molecular construction. Utilizing the established heterologous expression system, activation of the pathway-specific transcription factor coupled with a knockout strategy, and manipulating the global regulatory gene, the biosynthetic genes were exploited to activate biosynthetic pathways and decipher the encoded enzyme functions. We show that this methodology was beneficial for acquiring fungal treasures for drug discovery. These studies also enabled the investigation of the molecular function of natural products in fungal development.

scholarly journals Genome Mining as New Challenge in Natural Products Discovery

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 199 ◽  
Author(s):  
Luisa Albarano ◽  
Roberta Esposito ◽  
Nadia Ruocco ◽  
Maria Costantini
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Synthetic Biology ◽  
Anticancer Agents ◽  
Genome Mining ◽  
Bioactive Natural Products ◽  
Advantages And Disadvantages ◽  
A Genome ◽  
Living Organisms ◽  
Natural Drugs

Drug discovery is based on bioactivity screening of natural sources, traditionally represented by bacteria fungi and plants. Bioactive natural products and their secondary metabolites have represented the main source for new therapeutic agents, used as drug leads for new antibiotics and anticancer agents. After the discovery of the first biosynthetic genes in the last decades, the researchers had in their hands the tool to understand the biosynthetic logic and genetic basis leading to the production of these compounds. Furthermore, in the genomic era, in which the number of available genomes is increasing, genome mining joined to synthetic biology are offering a significant help in drug discovery. In the present review we discuss the importance of genome mining and synthetic biology approaches to identify new natural products, also underlining considering the possible advantages and disadvantages of this technique. Moreover, we debate the associated techniques that can be applied following to genome mining for validation of data. Finally, we review on the literature describing all novel natural drugs isolated from bacteria, fungi, and other living organisms, not only from the marine environment, by a genome-mining approach, focusing on the literature available in the last ten years.

scholarly journals Structural insights into the binding modes of viral RNA-dependent RNA polymerases using a function-site interaction fingerprint method for RNA virus drug discovery

2020 ◽  
Author(s):  
zheng zhao ◽  
Phil bourne
Keyword(s):  
Drug Discovery ◽  
Rna Virus ◽  
Specific Binding ◽  
Structural Characteristics ◽  
Binding Modes ◽  
Ligand Interaction ◽  
Starting Point ◽  
Binding Pockets ◽  
Targeted Drug ◽  
Targeted Drug Discovery

The COVID-19 pandemic speaks to the need for drugs that are not only effective but also remain so given the mutation rate of COVID-19. To this end, we describe a strategy to design potential drugs that target RNA-dependent RNA polymerase (RDRP), a common conserved component of RNA viruses. We combine an RDRP structure dataset and all RDRP-ligand interaction fingerprints into an RDRP-targeted drug discovery procedure. In so doing we reveal the ligand-binding modes and RDRP structural characteristics. Specifically, four types of binding modes with corresponding binding pockets were determined, suggesting two major potential sub-pockets available for drug discovery. We screened a drug dataset of approximately 8,000 compounds against these binding pockets and presented the top ten small molecules as a starting point in further exploring the prevention of virus replication. In summary, the binding characteristics determined here help rationalize RDRP targeted drug discovery and provide insights into the specific binding mechanisms.

Unleashing the Potential of Microbial Natural Products in Drug Discovery: Focusing on Streptomyces as Antimicrobials Goldmine

2021 ◽  
Vol 21 ◽  
Author(s):  
Himangini Bansal ◽  
Rajeev K. Singla ◽  
Sahar Behzad ◽  
Hitesh Chopra ◽  
Ajmer S. Grewal ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
Therapeutic Potential ◽  
Streptomyces Species ◽  
New Era ◽  
Screening Programs ◽  
Starting Point ◽  
Privileged Structures ◽  
Microbial Natural Products

: The natural product specialized metabolites produced by microbes and plants are the backbone of our current drugs. Ironically, we are in a golden age of understanding natural product biosynthesis, biochemistry, and engineering. These advances have the potential to usher in a new era of natural product exploration and development, taking full advantage of the unique and favorable properties of natural product compounds in drug discovery. There is now an increasing realization that these privileged structures represent the optimal starting point for the development of clinically viable assets. Here, we outline the current state-of-the-art in antimicrobial natural product drug discovery, specifically Streptomyces species, with a specific focus on how the emerging field of synthetic biology is delivering the tools and technologies required to unlock the therapeutic potential of natural products. We illustrate how these approaches are circumventing many of the problems that have historically plagued conventional screening programs, enabling the expedient discovery of new molecules with novel functions.

scholarly journals Structural insights into the binding modes of viral RNA-dependent RNA polymerases using a function-site interaction fingerprint method for RNA virus drug discovery

2020 ◽  
Author(s):  
zheng zhao ◽  
Phil bourne
Keyword(s):  
Drug Discovery ◽  
Rna Virus ◽  
Specific Binding ◽  
Structural Characteristics ◽  
Binding Modes ◽  
Ligand Interaction ◽  
Starting Point ◽  
Binding Pockets ◽  
Targeted Drug ◽  
Targeted Drug Discovery

The COVID-19 pandemic speaks to the need for drugs that are not only effective but also remain so given the mutation rate of COVID-19. To this end, we describe a strategy to design potential drugs that target RNA-dependent RNA polymerase (RDRP), a common conserved component of RNA viruses. We combine an RDRP structure dataset and all RDRP-ligand interaction fingerprints into an RDRP-targeted drug discovery procedure. In so doing we reveal the ligand-binding modes and RDRP structural characteristics. Specifically, four types of binding modes with corresponding binding pockets were determined, suggesting two major potential sub-pockets available for drug discovery. We screened a drug dataset of approximately 8,000 compounds against these binding pockets and presented the top ten small molecules as a starting point in further exploring the prevention of virus replication. In summary, the binding characteristics determined here help rationalize RDRP targeted drug discovery and provide insights into the specific binding mechanisms.

scholarly journals Natural Products as Modulators of Sirtuins

2020 ◽  
Author(s):  
Berin Karaman Mayack ◽  
Wolfgang Sippl ◽  
Fidele Ntie-Kang
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Histone Deacetylases ◽  
High Throughput Screening ◽  
Chemical Space ◽  
Class Iii ◽  
Drug Candidates ◽  
Starting Point ◽  
Recent Developments ◽  
Potent Drug

Natural products have been used for the treatment of human diseases since ancient history. Over time, due to the lack of precise tools and techniques for the separation, purification, and structural elucidation of active constituents in natural resources there has been a decline in financial support and efforts in characterization of natural products. Advances in the design of chemical compounds and the understanding of their functions is of pharmacological importance for the biomedical field. However, natural products regained attention as sources of novel drug candidates upon recent developments and progress in technology. Natural compounds were shown to bear an inherent ability to bind to biomacromolecules and cover an unparalleled chemical space in comparison to most libraries used for high-throughput screening. Thus, natural products hold a great potential for the drug discovery of new scaffolds for therapeutic targets such as Sirtuins. Sirtuins are Class III histone deacetylases that have been linked to many diseases such as Parkinson`s disease, Alzheimer’s disease, type II diabetes, and cancer linked to aging. In this review, we examine the revitalization of interest in natural products for drug discovery and discuss natural product modulators of Sirtuins that could serve as a starting point for the development of isoform selective and highly potent drug-like compounds.

scholarly journals Natural Products in Drug Discovery: Approaches and Development

2021 ◽  
pp. 93-110
Author(s):  
Pious Soris Tresina ◽  
Murugeswaran Santhiya Selvam ◽  
Authinarayanan Rajesh ◽  
Asirvatham Doss ◽  
Veerabahu Ramasamy Mohan
Keyword(s):  
Multiple Sclerosis ◽  
Natural Products ◽  
Drug Discovery ◽  
Cardiovascular Diseases ◽  
Pharmaceutical Industry ◽  
Natural Product ◽  
Lead Structure ◽  
Antiinflammatory Agents ◽  
Plant Sources ◽  
Molecular Biological Techniques

Historically, natural products (NP’s) have played a significant role in drug discovery, not only in cancer and infectious diseases, but also in other therapeutic  areas including cardiovascular diseases and multiple sclerosis. Profit and loss, Partnerships and averages, natural products also present certain challenges for drug discovery, such as technical obstacles to screening, isolation, characterization and optimization, which added to decline in their search by the pharmaceutical industry from the 1990s onwards. In recent days the applications of molecular biological techniques have increased the availability of novel compounds that can be conveniently produced in bacteria or yeast or plant sources. In addition to this, combinational chemistry approaches are being based on natural product scaffolds to create screening libraries that closely resemble drug-like compounds. Employing these technologies gives us a chance to execute research in screening new molecules by means of a software and data base to ascertain natural products as a major source for drug discovery. It lastly directs to lead structure discovery. This review discusses plant based natural product drug discovery and how innovative technologies play a role in next generation drug discovery and highlights from the published literature on plants as sources of antiinflammatory agents.   GRAPHICAL ABSTRACT

Sign in / Sign up

Export Citation Format

Share Document