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Current Opinion in Chemical Biology Feb 2014Glycan microarrays have become indispensable tools for studying protein-glycan interactions. Along with chemo-enzymatic synthesis, glycans isolated from natural sources... (Review)
Review
Glycan microarrays have become indispensable tools for studying protein-glycan interactions. Along with chemo-enzymatic synthesis, glycans isolated from natural sources have played important roles in array development and will continue to be a major source of glycans. N-glycans and O-glycans from glycoproteins, and glycans from glycosphingolipids (GSLs) can be released from corresponding glycoconjugates with relatively mature methods, although isolation of large numbers and quantities of glycans is still very challenging. Glycosylphosphatidylinositol (GPI) anchors and glycosaminoglycans (GAGs) are less represented on current glycan microarrays. Glycan microarray development has been greatly facilitated by bifunctional fluorescent linkers, which can be applied in a 'Shotgun Glycomics' approach to incorporate isolated natural glycans. Glycan presentation on microarrays may affect glycan binding by GBPs, often through multivalent recognition by the GBP.
Topics: Animals; Biological Products; Databases, Genetic; Glycomics; Glycoproteins; Glycosphingolipids; Humans; Polysaccharides
PubMed: 24487062
DOI: 10.1016/j.cbpa.2014.01.001 -
Natural Product Reports Aug 2017Covering: up to 2017.Natural products are important secondary metabolites produced by bacterial and fungal species that play important roles in cellular growth and... (Review)
Review
Covering: up to 2017.Natural products are important secondary metabolites produced by bacterial and fungal species that play important roles in cellular growth and signaling, nutrient acquisition, intra- and interspecies communication, and virulence. A subset of natural products is produced by nonribosomal peptide synthetases (NRPSs), a family of large, modular enzymes that function in an assembly line fashion. Because of the pharmaceutical activity of many NRPS products, much effort has gone into the exploration of their biosynthetic pathways and the diverse products they make. Many interesting NRPS pathways have been identified and characterized from both terrestrial and marine bacterial sources. Recently, several NRPS pathways in human commensal bacterial species have been identified that produce molecules with antibiotic activity, suggesting another source of interesting NRPS pathways may be the commensal and pathogenic bacteria that live on the human body. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) have been identified as a significant cause of human bacterial infections that are frequently multidrug resistant. The emerging resistance profile of these organisms has prompted calls from multiple international agencies to identify novel antibacterial targets and develop new approaches to treat infections from ESKAPE pathogens. Each of these species contains several NRPS biosynthetic gene clusters. While some have been well characterized and produce known natural products with important biological roles in microbial physiology, others have yet to be investigated. This review catalogs the NRPS pathways of ESKAPE pathogens. The exploration of novel NRPS products may lead to a better understanding of the chemical communication used by human pathogens and potentially to the discovery of novel therapeutic approaches.
Topics: Bacteria; Biological Products; Fungi; Humans; Molecular Structure; Peptide Synthases
PubMed: 28642945
DOI: 10.1039/c7np00029d -
Trends in Microbiology Dec 2016Genome sequencing has created unprecedented opportunities for natural-product discovery and new insight into the diversity and distributions of natural-product... (Review)
Review
Genome sequencing has created unprecedented opportunities for natural-product discovery and new insight into the diversity and distributions of natural-product biosynthetic gene clusters (BGCs). These gene collectives are highly evolved for horizontal exchange, thus providing immediate opportunities to test the effects of small molecules on fitness. The marine actinomycete genus Salinispora maintains extraordinary levels of BGC diversity and has become a useful model for studies of secondary metabolism. Most Salinispora BGCs are observed infrequently, resulting in high population-level diversity while conforming to constraints associated with maximum genome size. Comparative genomics is providing a mechanism to assess secondary metabolism in the context of evolution and evidence that some products represent ecotype-defining traits while others appear selectively neutral.
Topics: Actinobacteria; Biological Products; Computational Biology; Genetic Variation; Genome, Bacterial; Genomics; Multigene Family; Secondary Metabolism
PubMed: 27491886
DOI: 10.1016/j.tim.2016.07.006 -
Frontiers in Bioscience (Landmark... Jan 2019Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder among children and adults. Impulsivity, inattention, and hyperactivity are... (Review)
Review
Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder among children and adults. Impulsivity, inattention, and hyperactivity are hallmark of ADHD. While ADHD is not on the autism spectrum, they are related in several ways as they have some overlapping symptoms. The pathogenesis of ADHD has so far remained enigmatic, however, there is some evidence suggesting critical association among ADHD and the level of oxidative stress which trigger cell membrane damage, changes in inner structure and function of proteins, as well as structural damage to DNA which eventually culminate into development of ADHD. Although stimulants as well as some classes of non-stimulants are used to ameliorate symptom of ADHD, various adverse effects have been associated with such compounds. To date, treatment of ADHD is done with a combination of medications, behavior modifications, psycho-education, family therapy and life-style changes. The American Academy of Pediatrics officially promote stimulant medications and/or behavior therapy as 'first line of therapy'. In addition to the presently therapeutic armamentarium, evidences are emerging on relevancy of natural products. There has been an interest on the therapeutic role of antioxidants in the treatment of ADHD. The present review aims to highlight the beneficiary role played by different antioxidants in mitigating the symptoms of ADHD.
Topics: Adult; Antioxidants; Ascorbic Acid; Attention Deficit Disorder with Hyperactivity; Biological Products; Child; Glutathione; Humans; Oxidative Stress; Risk Factors
PubMed: 30468658
DOI: 10.2741/4720 -
Molecules (Basel, Switzerland) Aug 2020, popularly known as "Jucá" or "Pau-ferro", belongs to the Fabaceae family, and is classified as a native and endemic species in Brazil. Numerous studies that portray... (Review)
Review
, popularly known as "Jucá" or "Pau-ferro", belongs to the Fabaceae family, and is classified as a native and endemic species in Brazil. Numerous studies that portray its ethnobotany, chemical composition, and biological activities exist in the literature. The present study aimed to systematically review publications addressing the botanical aspects, uses in popular medicine, phytochemical composition, and bioactivities of . The searches focused on publications from 2015 to March 2020 using the Scopus, Periódicos Capes, PubMed, Google Scholar, and ScienceDirect databases. The leaves, fruits, seeds, and bark from are used in popular medicine to treat disorders affecting several systems, including the circulatory, immune, cardiovascular, digestive, respiratory, genitourinary, musculoskeletal, and conjunctive systems. The most commonly found chemical classes in phytochemical studies are flavonoids, polyphenols, terpenoids, tannins, saponins, steroids, and other phenolic compounds. The biological properties of the extracts and isolated compounds of most cited in the literature were antibacterial, antifungal, antioxidant, antiproliferative, anti-inflammatory, and healing potential. However, further studies are still needed to clarify a link between its traditional uses, the active compounds, and the reported pharmacological activities, as well as detailed research to determine the toxicological profile of .
Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antioxidants; Caesalpinia; Ethnobotany; Ethnopharmacology; Humans; Phytochemicals; Phytotherapy; Plant Extracts
PubMed: 32842529
DOI: 10.3390/molecules25173831 -
International Journal of Molecular... Feb 2024Black garlic (BG) is a fermented form of garlic (.), produced at precisely defined temperatures, humidities, and time periods. Although garlic has been used for... (Review)
Review
Black garlic (BG) is a fermented form of garlic (.), produced at precisely defined temperatures, humidities, and time periods. Although garlic has been used for thousands of years, black garlic is a relatively new discovery. There are many bioactive compounds in black garlic that give it medicinal properties, including anti-inflammatory and anti-cancer properties. In our review article, we present scientific studies examining the anti-inflammatory and anti-cancer effects of black garlic. According to research, this effect is mainly due to the reduction in the production of pro-inflammatory cytokines, as well as the ability to scavenge free oxygen radicals and induce apoptosis. In addition, the phytochemicals contained in it have antiproliferative and antiangiogenic properties and inhibit the growth of cancer cells. Black garlic is a valuable source of biologically active substances that can support anti-inflammatory and anti-cancer therapy. Compared to black garlic has fewer side effects and is easier to consume.
Topics: Humans; Garlic; Plant Extracts; Antioxidants; Neoplasms; Anti-Inflammatory Agents; Biological Products
PubMed: 38339077
DOI: 10.3390/ijms25031801 -
The Journal of Biological Chemistry Nov 2019Throughout history, natural products have significantly contributed to the discovery of novel chemistry, drug leads, and tool molecules to probe and address complex... (Review)
Review
Throughout history, natural products have significantly contributed to the discovery of novel chemistry, drug leads, and tool molecules to probe and address complex challenges in biology and medicine. Recent microbial genome sequencing efforts have uncovered many microbial biosynthetic gene clusters without an associated natural product. This means that the natural products isolated to date do not fully reflect the biosynthetic potential of microbial strains. This observation has rejuvenated the natural product community and inspired a return to microbial strain collections. Mining large microbial strain collections with the most current technologies in genome sequencing, bioinformatics, and high-throughput screening techniques presents new opportunities in natural product discovery. In this review, we report on the newly expanded microbial strain collection at The Scripps Research Institute, which represents one of the largest and most diverse strain collections in the world. Two complementary approaches, structure-centric and function-centric, are presented here to showcase how to leverage a large microbial strain collection for natural product discovery and to address challenges and harness opportunities for future efforts. Highlighted examples include the discovery of alternative producers of known natural products with superior growth characteristics and high titers, novel analogs of privileged scaffolds, novel natural products, and new activities of known and new natural products. We anticipate that this large microbial strain collection will facilitate the discovery of new natural products for many applications.
Topics: Adamantane; Aminobenzoates; Anilides; Bacteria; Biological Products; Computational Biology; Databases, Genetic; Fungi; Genome, Bacterial; Multigene Family
PubMed: 31570525
DOI: 10.1074/jbc.REV119.006514 -
Marine Drugs Sep 2022This review presents literature data: the history of the discovery of quinoid compounds, their biosynthesis and biological activity. Special attention is paid to the... (Review)
Review
This review presents literature data: the history of the discovery of quinoid compounds, their biosynthesis and biological activity. Special attention is paid to the description of the quinoid pigments of the sea urchins (from the family ) and (from the family ). The marine environment is considered one of the most important sources of natural bioactive compounds with extremely rich biodiversity. Primary- and some secondary-mouthed animals contain very high concentrations of new biologically active substances, many of which are of significant potential interest for medical purposes. The quinone pigments are products of the secondary metabolism of marine animals, can have complex structures and become the basis for the development of new natural products in echinoids that are modulators of chemical interactions and possible active ingredients in medicinal preparations. More than 5000 chemical compounds with high pharmacological potential have been isolated and described from marine organisms. There are three well known ways of naphthoquinone biosynthesis-polyketide, shikimate and mevalonate. The polyketide pathway is the biosynthesis pathway of various quinones. The shikimate pathway is the main pathway in the biosynthesis of naphthoquinones. It should be noted that all quinoid compounds in plants and animals can be synthesized by various ways of biosynthesis.
Topics: Animals; Strongylocentrotus; Mirabilis; Mevalonic Acid; Sea Urchins; Naphthoquinones; Polyketides; Biological Products; Pigments, Biological
PubMed: 36286435
DOI: 10.3390/md20100611 -
ACS Chemical Biology Dec 2021Graspetides are a class of ribosomally synthesized and post-translationally modified peptide natural products featuring ATP-grasp ligase-dependent formation of...
Graspetides are a class of ribosomally synthesized and post-translationally modified peptide natural products featuring ATP-grasp ligase-dependent formation of macrolactones/macrolactams. These modifications arise from serine, threonine, or lysine donor residues linked to aspartate or glutamate acceptor residues. Characterized graspetides include serine protease inhibitors such as the microviridins and plesiocin. Here, we report an update to Rapid ORF Description and Evaluation Online (RODEO) for the automated detection of graspetides, which identified 3,923 high-confidence graspetide biosynthetic gene clusters. Sequence and co-occurrence analyses doubled the number of graspetide groups from 12 to 24, defined based on core consensus sequence and putative secondary modification. Bioinformatic analyses of the ATP-grasp ligase superfamily suggest that extant graspetide synthetases diverged once from an ancestral ATP-grasp ligase and later evolved to introduce a variety of ring connectivities. Furthermore, we characterized thatisin and -thatisin, two graspetides related by conformational stereoisomerism from . Derived from a newly identified graspetide group, thatisin and -thatisin feature two interlocking macrolactones with identical ring connectivity, as determined by a combination of tandem mass spectrometry (MS/MS), methanolytic, and mutational analyses. NMR spectroscopy of thatisin revealed a conformation for a key proline residue, while molecular dynamics simulations, solvent-accessible surface area calculations, and partial methanolytic analysis coupled with MS/MS support a conformation for -thatisin at the same position. Overall, this work provides a comprehensive overview of the graspetide landscape, and the improved RODEO algorithm will accelerate future graspetide discoveries by enabling open-access analysis of existing and emerging genomes.
Topics: Biological Products; Computational Biology; Ligases; Molecular Conformation; Multigene Family; Peptides; Protein Processing, Post-Translational; Ribosomes; Serine Proteinase Inhibitors; Tandem Mass Spectrometry
PubMed: 34766760
DOI: 10.1021/acschembio.1c00672 -
Molecules (Basel, Switzerland) Jul 2021Limonene is a monoterpene confined to the family of , showing several biological properties such as antioxidant, anti-inflammatory, anticancer, antinociceptive and... (Review)
Review
Limonene is a monoterpene confined to the family of , showing several biological properties such as antioxidant, anti-inflammatory, anticancer, antinociceptive and gastroprotective characteristics. Recently, there is notable interest in investigating the pharmacological effects of limonene in various chronic diseases due to its mitigating effect on oxidative stress and inflammation and regulating apoptotic cell death. There are several available studies demonstrating the neuroprotective role of limonene in neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, epilepsy, anxiety, and stroke. The high abundance of limonene in nature, its safety profile, and various mechanisms of action make this monoterpene a favorable molecule to be developed as a nutraceutical for preventive purposes and as an alternative agent or adjuvant to modern therapeutic drugs in curbing the onset and progression of neurodegenerative diseases. This manuscript presents a comprehensive review of the available scientific literature discussing the pharmacological activities of limonene or plant products containing limonene which attribute to the protective and therapeutic ability in neurodegenerative disorders. This review has been compiled based on the existing published articles confined to limonene or limonene-containing natural products investigated for their neurotherapeutic or neuroprotective potential. All the articles available in English or the abstract in English were extracted from different databases that offer an access to diverse journals. These databases are PubMed, Scopus, Google Scholar, and Science Direct. Collectively, this review emphasizes the neuroprotective potential of limonene against neurodegenerative and other neuroinflammatory diseases. The available data are indicative of the nutritional use of products containing limonene and the pharmacological actions and mechanisms of limonene and may direct future preclinical and clinical studies for the development of limonene as an alternative or complementary phytomedicine. The pharmacophore can also provide a blueprint for further drug discovery using numerous drug discovery tools.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biological Products; Citrus; Drug Discovery; Humans; Limonene; Neurodegenerative Diseases; Neuroprotective Agents; Oils, Volatile; Oxidative Stress; Phytotherapy; Plant Extracts
PubMed: 34361686
DOI: 10.3390/molecules26154535