scholarly journals Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

2016 ◽  
Vol 12 ◽  
pp. 2325-2342 ◽  
Author(s):  
Darcy J Atkinson ◽  
Briar J Naysmith ◽  
Daniel P Furkert ◽  
Margaret A Brimble
Keyword(s):  
Natural Products ◽  
Amino Acid ◽  
Drug Discovery ◽  
Peptide Antibiotic ◽  
Peptide Antibiotics ◽  
Global Public Health ◽  
Development Of Resistance ◽  
Wide Range ◽  
Imminent Threat ◽  
Synthetic Approaches

Rising resistance to current clinical antibacterial agents is an imminent threat to global public health and highlights the demand for new lead compounds for drug discovery. One such potential lead compound, the peptide antibiotic teixobactin, was recently isolated from an uncultured bacterial source, and demonstrates remarkably high potency against a wide range of resistant pathogens without apparent development of resistance. A rare amino acid residue component of teixobactin, enduracididine, is only known to occur in a small number of natural products that also possess promising antibiotic activity. This review highlights the presence of enduracididine in natural products, its biosynthesis together with a review of analogues of enduracididine. Reported synthetic approaches to the cyclic guanidine structure of enduracididine are discussed, illustrating the challenges encountered to date in the development of efficient synthetic routes to facilitate drug discovery efforts inspired by the discovery of teixobactin.

scholarly journals Natural Cyclic Peptides as an Attractive Modality for Therapeutics: A Mini Review

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2080 ◽  
Author(s):  
Muna Abdalla ◽  
Lyndy McGaw
Keyword(s):  
Drug Discovery ◽  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
Pharmacological Properties ◽  
Biological Processes ◽  
Peptide Antibiotics ◽  
Natural Sources ◽  
Biological Targets ◽  
Naturally Occurring ◽  
Wide Range

Peptides are important biomolecules which facilitate the understanding of complex biological processes, which in turn could be serendipitous biological targets for future drugs. They are classified as a unique therapeutic niche and will play an important role as fascinating agents in the pharmaceutical landscape. Until now, more than 40 cyclic peptide drugs are currently in the market, and approximately one new cyclopeptide drug enters the market annually on average. Interestingly, the majority of clinically approved cyclic peptides are derived from natural sources, such as peptide antibiotics and human peptide hormones. In this report, the importance of cyclic peptides is discussed, and their role in drug discovery as interesting therapeutic biomolecules will be highlighted. Recently isolated naturally occurring cyclic peptides from microorganisms, sponges, and other sources with a wide range of pharmacological properties are reviewed herein.

scholarly journals An Overview of Synthetic Approaches towards of Nitration of α-Tetralones

2019 ◽  
Vol 16 (3) ◽  
pp. 189-197
Author(s):  
Aeysha Sultan ◽  
Abdul Rauf Raza ◽  
Mian Habib Ur Rehman Mehmood ◽  
Bushra Nisar ◽  
Syeda Laila Rubab ◽  
...  
Keyword(s):  
Natural Products ◽  
Functional Groups ◽  
Pharmacological Agents ◽  
Wide Range ◽  
Synthetic Approaches

The 1-tetralone scaffold and its derivatives are not only important as pharmacological agents but these also serve as precursors for natural products and compounds of medicinal importance. The easiest way to introduce a substituent on an aromatic as well as aliphatic system is nitration. Once introduced, the –NO2 group can be easily replaced by a wide range of functional groups. The review aims to highlight strategies for nitration of substituted and unsubstituted 1-tetralone which led to introduction of NO2 functionality at various positions.

scholarly journals Peptide Antibiotic Sensing and Detoxification Modules ofBacillus subtilis

2010 ◽  
Vol 55 (2) ◽  
pp. 515-525 ◽  
Author(s):  
Anna Staroń ◽  
Dora Elisabeth Finkeisen ◽  
Thorsten Mascher
Keyword(s):  
Abc Transporter ◽  
Regulatory Sequences ◽  
Peptide Antibiotic ◽  
Peptide Antibiotics ◽  
Two Component System ◽  
Cationic Antimicrobial Peptide ◽  
Component System ◽  
Lipid Ii ◽  
Wide Range ◽  
Two Component

ABSTRACTPeptide antibiotics are produced by a wide range of microorganisms. Most of them target the cell envelope, often by inhibiting cell wall synthesis. One of the resistance mechanisms against antimicrobial peptides is a detoxification module consisting of a two-component system and an ABC transporter. Upon the detection of such a compound, the two-component system induces the expression of the ABC transporter, which in turn removes the antibiotic from its site of action, mediating the resistance of the cell. Three such peptide antibiotic-sensing and detoxification modules are present inBacillus subtilis. Here we show that each of these modules responds to a number of peptides and confers resistance against them. BceRS-BceAB (BceRS-AB) responds to bacitracin, plectasin, mersacidin, and actagardine. YxdJK-LM is induced by a cationic antimicrobial peptide, LL-37. The PsdRS-AB (formerly YvcPQ-RS) system responds primarily to lipid II-binding lantibiotics such as nisin and gallidermin. We characterized thepsdRS-ABoperon and defined the regulatory sequences within the PpsdApromoter. Mutation analysis demonstrated that PpsdAexpression is fully PsdR dependent. The features of both the PbceAand PpsdApromoters make them promising candidates as novel whole-cell biosensors that can easily be adjusted for high-throughput screening.

scholarly journals Discovery of Antimalarial Drugs from Streptomycetes Metabolites Using a Metabolomic Approach

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Siti Junaidah Ahmad ◽  
Mohd Badrin Hanizam Abdul Rahim ◽  
Syarul Nataqain Baharum ◽  
Mohd Shukri Baba ◽  
Noraziah Mohamad Zin
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Bioactive Compounds ◽  
Antimalarial Activity ◽  
Classical Method ◽  
Biologically Active ◽  
Gram Positive Bacteria ◽  
H Nmr ◽  
Wide Range ◽  
Bioassay Guided Fractionation

Natural products continue to play an important role as a source of biologically active substances for the development of new drug.Streptomyces, Gram-positive bacteria which are widely distributed in nature, are one of the most popular sources of natural antibiotics. Recently, by using a bioassay-guided fractionation, an antimalarial compound, Gancidin-W, has been discovered from these bacteria. However, this classical method in identifying potentially novel bioactive compounds from the natural products requires considerable effort and is a time-consuming process. Metabolomics is an emerging “omics” technology in systems biology study which integrated in process of discovering drug from natural products. Metabolomics approach in finding novel therapeutics agent for malaria offers dereplication step in screening phase to shorten the process. The highly sensitive instruments, such as Liquid Chromatography-Mass Spectrophotometry (LC-MS), Gas Chromatography-Mass Spectrophotometry (GC-MS), and Nuclear Magnetic Resonance (1H-NMR) spectroscopy, provide a wide range of information in the identification of potentially bioactive compounds. The current paper reviews concepts of metabolomics and its application in drug discovery of malaria treatment as well as assessing the antimalarial activity from natural products. Metabolomics approach in malaria drug discovery is still new and needs to be initiated, especially for drug research in Malaysia.

A Common Mechanism for Transport of Di- and Tri-Peptides by Hamster Jejunum in Vitro

1975 ◽  
Vol 49 (4) ◽  
pp. 313-322
Author(s):  
Jill M. Addison ◽  
D. Burston ◽  
Judith A. Dalrymple ◽  
D. M. Matthews ◽  
J. W. Payne ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Transport System ◽  
Amino Acid Residue ◽  
Biologically Active ◽  
Common Mechanism ◽  
Peptide Antibiotic ◽  
Uptake Mechanism ◽  
Wide Range

1. This paper describes the results of a survey of the effects of peptides and amino acids on uptake by rings of everted hamster jejunum in vitro of glycylsarcosylsarcosine, a tripeptide which is taken up by an active mechanism but is very resistant to hydrolysis, appearing intact in the rings. The results of a small number of similar experiments with β-alanylglycylglycine, another tripeptide which is taken up with very little hydrolysis, are also described. 2. Uptake of the two tripeptides was inhibited by other di- and tri-peptides, but not by free amino acids. The results suggest that dipeptides and tri-peptides share a common uptake mechanism. The tetrapeptide glycylsarcosylsarcosylsarcosine did not inhibit uptake of glycylsarcosylsarcosine, and appears to be unable to utilize the uptake mechanism. 3. The results add to information about the influence of molecular structure on intestinal uptake of peptides by the system used by glycylsarcosylsarcosine, which is shared by a wide range of other di- and tri-peptides. In conjunction with previous results, they suggest that substitution of the N-terminal amino or C-terminal carboxyl groups reduces affinity for transport, that the presence of a β-amino acid residue in a peptide is tolerated by the transport system, and that the presence of a d-amino acid residue reduces affinity for transport. Some peptides containing or made up of basic or acidic amino acid residues appear to have a low affinity for the transport system used by glycylsarcosylsarcosine. 4. Of two biologically active peptides, one, cephalexin, a peptide antibiotic, inhibited uptake of glycylsarcosylsarcosine and is probably transported by the same system. The other, prolylleucylglycineamide, which has the action of a hypothalamic regulatory factor, did not, and its structural features may make it unsuitable for carrier-mediated transport by the small intestine.

scholarly journals Application of Amino Acids in the Structural Modification of Natural Products: A Review

2021 ◽  
Vol 9 ◽  
Author(s):  
Qian Xu ◽  
Hao Deng ◽  
Xiaoting Li ◽  
Zhe-Shan Quan
Keyword(s):  
Amino Acids ◽  
Natural Products ◽  
Drug Discovery ◽  
Adverse Effects ◽  
Theoretical Basis ◽  
Structural Modification ◽  
Poor Solubility ◽  
Wide Range ◽  
The Future ◽  
Low Activity

Natural products and their derivatives are important sources for drug discovery; however, they usually have poor solubility and low activity and require structural modification. Amino acids are highly soluble in water and have a wide range of activities. The introduction of amino acids into natural products is expected to improve the performance of these products and minimize their adverse effects. Therefore, this review summarizes the application of amino acids in the structural modification of natural products and provides a theoretical basis for the structural modification of natural products in the future. The articles were divided into six types based on the backbone structures of the natural products, and the related applications of amino acids in the structural modification of natural products were discussed in detail.

scholarly journals Thiopeptide antibiotics stimulate biofilm formation in Bacillus subtilis

2015 ◽  
Vol 112 (10) ◽  
pp. 3086-3091 ◽  
Author(s):  
Rachel Bleich ◽  
Jeramie D. Watrous ◽  
Pieter C. Dorrestein ◽  
Albert A. Bowers ◽  
Elizabeth A. Shank
Keyword(s):  
Natural Products ◽  
Bacillus Subtilis ◽  
Secondary Metabolites ◽  
Bacterial Species ◽  
Imaging Mass Spectrometry ◽  
Gene Clusters ◽  
Peptide Antibiotics ◽  
Wide Range ◽  
Thiopeptide Antibiotics ◽  
Peptide Gene

Bacteria have evolved the ability to produce a wide range of structurally complex natural products historically called “secondary” metabolites. Although some of these compounds have been identified as bacterial communication cues, more frequently natural products are scrutinized for antibiotic activities that are relevant to human health. However, there has been little regard for how these compounds might otherwise impact the physiology of neighboring microbes present in complex communities. Bacillus cereus secretes molecules that activate expression of biofilm genes in Bacillus subtilis. Here, we use imaging mass spectrometry to identify the thiocillins, a group of thiazolyl peptide antibiotics, as biofilm matrix-inducing compounds produced by B. cereus. We found that thiocillin increased the population of matrix-producing B. subtilis cells and that this activity could be abolished by multiple structural alterations. Importantly, a mutation that eliminated thiocillin’s antibiotic activity did not affect its ability to induce biofilm gene expression in B. subtilis. We go on to show that biofilm induction appears to be a general phenomenon of multiple structurally diverse thiazolyl peptides and use this activity to confirm the presence of thiazolyl peptide gene clusters in other bacterial species. Our results indicate that the roles of secondary metabolites initially identified as antibiotics may have more complex effects—acting not only as killing agents, but also as specific modulators of microbial cellular phenotypes.

Comparative Study on Mitogen Activated Protein Kinase of Plasmodium Species by Using in silico Method

2012 ◽  
Vol 9 (1) ◽  
pp. 1
Author(s):  
Mohd Fakharul Zaman Raja Yahya ◽  
Hasidah Mohd Sidek
Keyword(s):  
Amino Acid ◽  
In Silico ◽  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Plasmodium Species ◽  
Mitogen Activated Protein Kinase ◽  
Multiple Sequence ◽  
Wide Range ◽  
Mitogen Activated Protein ◽  
Human Plasmodium

Malaria parasites, Plasmodium can infect a wide range of hosts including humans and rodents. There are two copies of mitogen activated protein kinases (MAPKs) in Plasmodium, namely MAPK1 and MAPK2. The MAPKs have been studied extensively in the human Plasmodium, P. falciparum. However, the MAPKs from other Plasmodium species have not been characterized and it is therefore the premise of presented study to characterize the MAPKs from other Plasmodium species-P. vivax, P. knowlesi, P. berghei, P. chabaudi and P.yoelli using a series of publicly available bioinformatic tools. In silico data indicates that all Plasmodium MAPKs are nuclear-localized and contain both a nuclear localization signal (NLS) and a Leucine-rich nuclear export signal (NES). The activation motifs of TDY and TSH were found to be fully conserved in Plasmodium MAPK1 and MAPK2, respectively. The detailed manual inspection of a multiple sequence alignment (MSA) construct revealed a total of 17 amino acid stack patterns comprising of different amino acids present in MAPKJ and MAPK2 respectively, with respect to rodent and human Plasmodia. It is proposed that these amino acid stack patterns may be useful in explaining the disparity between rodent and human Plasmodium MAPKs. 

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