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Synthesis of Bioactive Peptides for Pharmaceutical Applications
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Jaison Jeevanandam, Ashish Kumar Solanki, Shailza Sharma, Prabir Kumar Kulabhusan, Sapna Pahil, Michael K. Danquah
Burns and their associated wounds are an important public health problem throughout the world. The conventional curative therapies for burn wounds have drawbacks of increasing antibiotic resistance to the common pathogenic bacteria such as S. aureus, A. baumannii, and P. aeruginosa. Thus, antimicrobial peptides with a broad activity spectrum are a capable alternative for surgical wound treatments, burns, and other skin infections. For instance, human AMP cathelicidin (LL-37) controls inflammation and promotes wound healing by stimulating fibroblasts and epidermal cells to form a granulation tissue and thus promoting angiogenesis. Likewise, synthetic peptide LLKKK18 conjugated with dextrins not only was effective in wound healing but also promoted angiogenesis in C57-BL/6 mice. Similarly, Pexiganan, which is a promising derivative of antimicrobial magainin peptide, is efficient against 200 bacteria of Gram-positive and Gram-negative strains. Various synthetic peptides, such as HB107, HB1345, PXL-150, Novispirin G10, IK8L, D2A21, and SHAP1, were also delivered in burn wounds as nano-emulsions, which showed potential antimicrobial property against P. aeruginosa in preclinical and clinical trials. Moreover, a synthetic peptide called SHAP-1 promoted wound healing at a very low concentration and is reported to be stable, even when high salt concentrations and proteases are present (Lee et al., 2014). Another synthetic peptide, Novispirin-G10, is reported to possess rapid bacterial inhibition ability in partial-thickness burn wounds that are infected by P. aeruginosa. Further, a novel antimicrobial peptide (A3-APO), as either a dimer or a monomer, was found effective against wounds and skin burn infections caused by multi-drug-resistant strains of Acinetobacter baumannii (Javia et al., 2018; Heinbockel et al., 2018).
Mycotoxicosis – diagnosis, prevention and control: past practices and future perspectives
Published in Toxin Reviews, 2020
Peptides do not alter the morphology or flowering of transgenic plants (Cary et al.2000, DeGray et al.2001, Mitsuhara et al.2006). Many peptides have been identified having antifungal as well as antibacterial properties. The defensin gene isolated from mustard plant when introduced in tobacco and peanut resulted in resistant growth of many fungi like Fusarium moniliformis and Phytophthora parasitica (Anuradha et al.2008). Magainin analog isolated from amphibians when introduced in tobacco resulted in fungal as well as bacterial control (Li et al. 2001). Various synthetic peptides have been redesigned from natural sources having antifungal effects like D5C (Weissinger et al. 1999), D4E1 (Rajasekaran et al. 2005, 2008), MSI-99 (Alan et al. 2004), and analog of magainin MSI-99 (Chakrabarti et al. 2003). Genetic engineering of plants or preparation of transgenic crops is an ongoing investigation and wide-scale commercialization is yet to be seen for the prevention of mycotoxin production at preharvest stages.
Antimicrobial peptides (AMPs): a patent review (2015–2020)
Published in Expert Opinion on Therapeutic Patents, 2020
Giannamaria Annunziato, Gabriele Costantino
Antimicrobial peptides are recognized as a possible source of drugs for the treatment of antibiotic-resistant bacterial infections [23]. Studies on the mechanism of action of natural and synthetic peptides in model systems have contributed greatly in the identification of parameters required for antimicrobial activity. More than 2800 natural peptides are known to date and they display lots differences in their amino acid composition and length, and for these reasons it is hard to identify a common shared template that could be considered necessary to exert antimicrobial activity [24]. It is possible to point out several structural characteristics that are crucial for antimicrobial activity. A great number of AMPs show a net positive charge that enable electrostatic interactions to negatively charged cell membrane of bacteria, for this reason they are at the same time inactive toward the neutral membrane of mammalian cells. Indeed, the net charge of known natural AMPs varies widely from +16 to −6 [25]. The most of identified AMPs have an intermediate net positive charge around +6. This evidence could be directly correlated with peptide potency and selectivity, so higher or lower values outside this range can result in reduced activity toward bacterial cells and/or increased toxicity toward host cells. The relationship between these parameters and function has been proved by Dathe et al. [26] They have shown that increasing the charge of magainin analogs above +5 resulted in both increased hemolysis and loss of antimicrobial potency. The amphipathic nature of AMPs determines their conformational flexibility. They can form secondary structures, like ⍺-helices, ß-sheets or a mixture of both, upon binding and penetration of bacterial cell membrane [27].
Design of α-helical antimicrobial peptides with a high selectivity index
Published in Expert Opinion on Drug Discovery, 2019
To conclude this section, Figure 1 left panel illustrates examples of natural and designed peptides with a high selectivity and mostly high activity against E. coli, while Figure 1 right panel shows that the same peptides can act as wide spectrum antibiotics or can be essentially inactive against Gram-positives. This is seen in more details when E. coli and S. aureus overall performance parameter PE (Figure 2. left panel) and relative overall performance parameter APEX (Figure 2. right panel) are plotted as x and y coordinate for each peptide. Natural magainin 2 peptide and its pexiganan analogue have respectively coordinates (0.4, 0.1) and (17.4, 4.5) at Figure 2 left panel. Most peptides from Table 1 have better overall performance against S. aureus than magainin-2 and all peptides from Table 1 have better overall performance against E. coli. Magainin 2 served through years as an amazingly good source for creating its more potent and sometimes equally nontoxic analogues. This observation opens good prospects for AMP designers to start with any other of Table 1 peptides in the direction of improving their performance either against Gram-positives (going toward higher Figure 2 y-values) or against Gram-negatives (going toward higher Figure 2 x-values). Nevertheless, it is not an easy job to achieve an order of magnitude improvement in overall performance with respect to pexiganan as the yardstick example of an excellent peptide antibiotic (Figure 2 right panel). This goal has been achieved by very few of designed peptides irrespective of their length. Natural helical peptides are as a rule weaker in overall performance than pexiganan. This is the reason why we do not see them (with one exception) at Figure 2. right panel (full circles). If they are very good against E. coli the opposite is true with their activity against S aureus. Apparently, biological host-pathogen coevolution favored the development of AMPs with a high specific activity only against particularly troublesome bacterial strains for the host organism.