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The Journey through the Gene: a Focus on Plant Anti-pathogenic Agents Mining in the Omics Era
Published in Mahendra Rai, Chistiane M. Feitosa, Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
José Ribamar Costa Ferreira-Neto, Éderson Akio Kido, Flávia Figueira Aburjaile, Manassés Daniel da Silva, Marislane Carvalho Paz de Souza, Ana Maria Benko-Iseppon
Plant AMPs have been isolated from several tissues (roots, seeds, flowers, stems and leaves) from a broad number of species (Nawrot et al. 2014). They comprise different classes, including thionins, defensins, lipid transfer proteins, hevein-like peptides, knottins and cyclotides. Plant AMPs and SM-PAAs are promising antimicrobial agents with important biotechnological applications, such as drug development against human pathogenic organisms.
Role of Engineered Proteins as Therapeutic Formulations
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Khushboo Gulati, Krishna Mohan Poluri
Cystine knot mini proteins (Knottins) are 30–50-amino-acid-long small proteins comprising a canonical cysteine knot. Structurally, knottins contain three antiparallel β-strands and are stabilized by three disulfide bonds arranged in a unique fashion. These bonds are formed between cys1 to cys 4, cys2 to cys5, and cys3 to cys6. The disulfide bond between cys3 to cys6 crosses a macrocycle formed by other two disulfide bonds and a backbone peptide bond. Together, these bonds form a cystine knot structure. Such a structure is responsible for higher thermal, chemical, and proteolytic stability of knottins. Cyclotides are a class of cystine knot proteins that undergo head to tail cyclization due to the presence of an extra loop in their structural architecture. Both knottins and cyclotides serve as promising candidates for potential therapeutic applications. External loops of both knottins and cyclotides make them amenable to various amino acid substitutions and also to the addition of various amino acids, rendering them structurally stable (Moore et al., 2012).
Impact of Nutrition and Dietary Supplementation on Psoriasis Pathology
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Odete Mendes, Mithila Shitut, Jayson Chen
Viola tricolor has immunosuppressive and anti-inflammatory properties. It contains flavonoids, polysaccharides, phyenylcarbonic acids, salicylic acid derivatives, catechins, and cumarins, as well as macrocyclic peptides–cyclotides. Cyclotides are ribosomal synthesized plant compounds reported to have immunosuppressive properties that can impact proliferation of T lymphocytes (Grundemann et al., 2012). An aqueous extract of V. tricolor inhibited the secretion of IL-2 without impacting the expression of IL-R2 receptor. Additionally, it also reduced IFN-γ and TNF-α, potentially impacting disease progression (Hellinger et al., 2014).
How can we improve peptide drug discovery? Learning from the past
Published in Expert Opinion on Drug Discovery, 2021
Another approach being developed in parallel is the use of plants for peptide production. Specifically, many cyclic peptides such as cyclotides are naturally produced in plants and in future modified ‘designer’ cyclic peptides might be produced in such plant biofactories by the inclusion of the appropriate precursor genes. For example, a potent plasmin inhibitor was recently produced in a rapid and scalable approach in the plant Nicotiana benthamiana [35]. This host plant is readily able to be genetically transformed and is amenable to transient expression. It was used for example to express an antibody treatment during the Ebola outbreak in 2014. We note that plant-based expression is not likely to become the main route of manufacture of peptides but that it may be well suited to certain applications. In our own work, for example, we are exploring options for selectively producing therapeutic peptides in plant seeds, whereby the seed could effectively become a ‘biopill.’
Antimicrobial peptides: a promising strategy for lung cancer drug discovery?
Published in Expert Opinion on Drug Discovery, 2020
Farshid Zandsalimi, Sam Talaei, Mehdi Noormohammad Ahari, Shahin Aghamiri, Pourya Raee, Soheil Roshanzamiri, Fatemeh Yarian, Mojgan Bandehpour, Zeinab Zohrab Zadeh
The antitumor activity of host AMPs has been established by several studies, but because of poor cytotoxic activity, they cannot be directly used as antitumor agents. The anticancer efficacy of candidate ACPs can be improved depending on their mechanism. For instance, cyclotides exert their killing activity by targeting phosphatidylethanolamine phospholipids. Thus, novel analogs could be developed to enhance the membrane-binding specificities and selectivity to tumor cells by altering their amino acid compositions. Tian et al. [106] revealed that mutagenesis on particular AMPs can be useful for the induction of anticancer features. They substituted Glu16 of cathelicidin-BF (BF-30) with a Lys residue. The resulting peptide (Cbf-K16) exhibited a selective inhibitory effect on the proliferation of H460 human non-small cell lung cancer cells. The team postulated that Cbf-K16 made membrane rupture. The positive charge of Cbf-K16 also facilitates the binding of this antimicrobial peptide to genomic DNA and blocking gene expression. In another study, Huang et al. [107] used an engineered form of cecropin B (CB1a) on lung cancerous cells, in vivo and in vitro model. Their observations indicated that CB1a can disrupt adherence of tumor cells and significantly reduce their viability by inducing cell surface damages. Along with high toxicity to cancer cells, CB1a had less effect on the healthy cell when compared to docetaxel as a conventional drug in lung cancer therapy.
Chemical composition and broad-spectrum anthelmintic activity of a cultivar of toothache plant, Acmella oleracea, from Mizoram, India
Published in Pharmaceutical Biology, 2020
Pawi Bawitlung Lalthanpuii, Kholhring Lalchhandama
Highly lipophilic in nature, albendazole is one of the most diffusible anthelmintic molecules through the cuticle of nematodes. This property is important in drug action because the cuticle is chemically a highly specialized proteinaceous complex and is impermeable to most molecules. It has been shown that the drug enters through the cuticle of Haemonchus contortus and Ascaris suum by passive diffusion (Alvarez et al. 2007). In the cuticular and the underlying muscle tissues, albendazole prevents polymerization of microtubules by competitively binding to β-tubulins to cause paralysis and death (Abongwa et al. 2017). Ivermectin diffuse through the cuticle and effectively inhibits muscle contraction in Caenorhaditis elegans, H. contortus and Oncocerca ochengi (Yates et al. 2003). Cyclotides, a family of plant peptides, are known to directly attack the cuticle of H. contortus and Trichostrongylus colubriformis (Colgrave et al. 2010). Natural cysteine proteinases are also found to cause disintegration of the cuticular proteins in different nematodes (Luoga et al. 2015). Therefore, our observations on the structural changes on the cuticle of A. perspicillum indicate that A. oleracea also directly targets the cuticle to cause deleterious anthelmintic effects.