Microalgae and Cyanobacteria as a Potential Source of Anticancer Compounds
Gokare A. Ravishankar, Ranga Rao Ambati in Handbook of Algal Technologies and Phytochemicals, 2019
A wide range of biologically active peptides isolated from microalgae and cyanobacteria are known to possess great therapeutic potential, and these have attracted much interest from the pharmaceutical industries (Gerwick and Moore 2012). These peptides from microalgae usually consist of 10–20 amino-acid residues and can be released by solvent extraction, enzymatic hydrolysis or microbial fermentation (Giordano et al. 2018). There are distinct structural classes of peptides, which include linear peptides, linear depsipeptides, linear lipopeptides, cyclic peptides, cyclic depsipeptides and cyclic lipopeptides (Mi et al. 2017). In terms of biosynthesis, some peptides are synthesized by a multiple enzyme system, such as nonribosomal peptide synthetase (NRPS) or polyketide synthase hybrid (NRPS/PKS) pathways, while other peptides are gene-coded, ribosomally synthesized and posttranslationally modified. Marine cyanobacteria represent a rich source of peptide metabolites in terms of structure and bioactivity. For instance, programs for drug discovery from marine cyanobacteria, such as the Panama International Cooperative Biodiversity Group (ICGB) program, have discovered more than 400 new peptide compounds between 2007 and 2016 (Mi et al. 2017). Many of the bioactive peptides derived from cyanobacteria were found to display anticancer activity.
New Strategies to Discover Non-Ribosomal Peptides as a Source of Antibiotics Molecules
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
The advance in experimental techniques, such as mass spectrometry, has allowed us to combine the in silico approaches with the experimental ones. An example of these new strategies was the study carried out by Vater et al. (2018); using bioinformatics and mass spectrometry techniques, these authors analyzed the genome of Paenibacillus polymyxa strain E681 to find NRPSs. They detected four gene clusters for the production of NRPs corresponding to four lipopeptide families, encoding fusaricidins, polymyxins, tridecaptins, and a yet unknown lipoheptapeptide designated as paenilipoheptin. These lipopeptides are cyclic compounds which contain a C12–13-beta-amino fatty acid integrated into the peptide ring (Vater et al., 2018). The cyclical structure of the majority of NRPs has made it difficult to identify them using traditional methods that have been developed for the identification of linear peptides; hence, bioinformatics methods have been used to identify them such as NRPquest which couples mass spectrometry and genome mining for the identification of NRPs (Mohimani et al., 2014).
Candida
Dongyou Liu in Handbook of Foodborne Diseases, 2018
A relatively new group of antifungal drugs introduced into clinical use at the beginning of the twenty-first century are cyclic lipopeptides–echinocandins.22,60,62 Originally derived from natural lipopeptides produced by Aspergillus rugulovalvus, Zalerion arboricola, and Papularia sphaerosperma, they are now available in the form of semisynthetic derivatives.60,62 Three echinocandins (caspofungin, micafungin, and anidulafungin) are the only available antifungal drugs targeting the cell wall. They act as noncompetitive inhibitors of β-(1,3)-D-glucan synthase enzyme complex, specifically targeting the FsK1 subunit. This enzyme is responsible for synthesis of 1,3-β-glucan, which is a crucial component that strengthens the cell wall. Lack of the glucan component disrupts the structure of growing cell walls and leads to osmotic instability and cell lysis.22,60,62 This target is very attractive due to the absence of homologous enzymes in mammalian cells, a high degree of selectivity for yeast, low toxicity for host cells, and minimal interactions with other drugs. However, they have a short half-life.60,62 Echinocandins are used for the treatment of invasive candidiasis and esophageal candidiasis and against azoles-resistant strains. Additionally, caspofungin is approved for invasive aspergillosis. Echinocandins are mainly used in hospital treatment. Furthermore, the modern nature of these groups of drugs and difficult accessibility add to the reliability of the antibiotics in Candida sp. treatment. Probably, the yeast had not yet produced resistance to this group of drugs.
Strong inhibitory activities and action modes of lipopeptides on lipase
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Mei-chun Chen, Tian-tian Liu, Jie-ping Wang, Yan-ping Chen, Qing-xi Chen, Yu-jing Zhu, Bo Liu
The lipopeptides produced from the strain FJAT-52631 were identified using the LC-QTOF-MS/MS method. Results revealed that three sets of homologue molecules with retention times in the range of 12.2–21.5, 27.0–38.7, and 45.2–54.0 min could be categorised as iturins, fengycins, and surfactins, respectively. Peptide sequences of each lipopeptide group were determined based on previous literature reports24–26. The retention times, MS and MS2 spectral data, and identification results were summarised, as shown in Table 1; the iturins consisted of C14–C16 iturin A; the surfactins consisted of C12–C16 surfactin A, and C16 surfactin A derivative; further, the fengycins consisted of C16/C18 fengycin A, C16 fengycin A2/B2, C16–C17 fengycin B, and C15 fengycin A/B derivatives. The iturin, fengycin, and surfactin content in the supernatant were calculated as 2.66 ± 1.50, 86.95 ± 4.08, and 35.93 ± 2.28 mg/L, respectively. The results demonstrated that fengycin was the most abundant lipopeptide family that was produced by the strain FJAT-52631.The lipopeptide production from Bacillus spp. firstly depends on itself. For example, the B. subtilis SPB1 strain have the ability to coproduce iturins, fengycins, and surfactins and highest content of surfactin in lipopeptide mixture was observed15.
Biotherapeutic effect of cell-penetrating peptides against microbial agents: a review
Published in Tissue Barriers, 2022
Idris Zubairu Sadiq, Aliyu Muhammad, Sanusi Bello Mada, Bashiru Ibrahim, Umar Aliyu Umar
A diverse group of CPPs from the genome of SARS-CoV-2, have been found in the proteomes of this virus.104 A computational screening has identified two possible peptides (HYWWT and HHYWH) that have a higher affinity for SARS-CoV-2 main proteases than human proteases using a computational screening,105 thus providing a basis for peptide-based COVID-19 drugs designed. A lipopeptide that works as a transmission-blocking peptide has also been reported.106 Accordingly, administration of this peptide as an intranasal serve as prophylactic against SARS-CoV-2 protecting ferret-to-ferret transmission.106 Another lipopeptide generated from SARS-C-terminal CoV-2’s heptad repeats (HRC) domain has been reported to block SARS-CoV-2 from spreading into human airway epithelial (HAE) cells, an ex vivo model that mimics respiratory virus propagation in patients.107 According to a study, a peptide (P9R) works against respiratory viruses including SARS-CoV-2 and influenza virus by attaching directly and inhibiting virus-host endosomal acidification.108 A peptide-based vaccination has also been developed using high-throughput molecular dynamics modeling to find T-cell and B-cell recognized epitopes for generating targeted antibodies against SARS-CoV-2.109 Short peptides for blocking the interaction of SARS-CoV-2 with angiotensin-converting enzyme 2 have also been proposed as effective COVID-19 treatments.110
Novel temporin L antimicrobial peptides: promoting self-assembling by lipidic tags to tackle superbugs
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Rosa Bellavita, Annarita Falanga, Elisabetta Buommino, Francesco Merlino, Bruno Casciaro, Floriana Cappiello, Maria Luisa Mangoni, Ettore Novellino, Maria Rosaria Catania, Rossella Paolillo, Paolo Grieco, Stefania Galdiero
The spontaneous organisation of molecules into ordered aggregates through supramolecular interactions, known as self-assembly, can be achieved by the rational design. In this context, lipopeptides represent an interesting approach and can be exploited to increase hydrophobicity, favour self-assembly, and boost membrane binding to strongly enhance antimicrobial activity and reduce toxicity against human cells. Residues containing long acyl chains can insert into lipid membranes despite the composition of the latter and induce non-selective, membrane destabilisation. It was also previously shown that single lysine residue attached to palmitic acids are not active, which further supports the view that activity is not only dictated by hydrophobicity but also requires a specific peptide sequence51; moreover, it is clear that also the organisation of the lipopeptides in solution and when bound to specific membranes is crucial for activity51. The lack of selectivity makes many lipopeptides toxic and consequently restricts their use to critical conditions for which other antibiotics are ineffective rendering important to finely tune also the positive charges of the designed compound.
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