Computational Design of Highly Selective Antimicrobial Peptides

Juretić, Davor; Vukičević, Damir; Ilić, Nada; Antcheva, Nikolinka; Tossi, Alessandro

doi:10.1021/ci900327a

Cited by 79 publications

(82 citation statements)

References 34 publications

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“…Sometimes, negatively charged residues are present on the polar face, but the reason why so many AMPs contain negatively charged residues remains unknown (37)(38)(39). Also, in our case, the substitution of the aspartic acid with alanine reduces activity, indicating that this position has to be occupied by a charged residue.…”

Section: Discussionmentioning

confidence: 69%

“…Gly 1 plays a key role; in fact, it is believed to improve the stability of peptides (49) and also is important for selectivity, as recently reported by Juretic et al (37). Moreover, most AMPs start with a Gly.…”

Section: Discussionmentioning

confidence: 87%

“…Aromatic residues are rare in AMPs and are mostly found near the N terminus (37)(38)(39). Aromatic residues have the unique property of being able to interact with the interfacial region of a membrane, thereby anchoring the peptide to the bilayer surface, and they are very common in viral fusion peptides ␤N (i,i ϩ x), respectively, whereas d ␣␤ (i,i ϩ 3) denotes a NOE cross-peak between the H␣ and H␤ protons of the i and i ϩ 3 residues, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…It is widely accepted that after reaching the microbial cytoplasmic membrane, AMPs initially interact with the negatively charged head groups of the external leaflet and then assume an amphipathic helical conformation that allows them to insert the hydrophobic face into the bilayer (37-39, 46, 47). The formation of the ␣-helical structure before membrane interaction may not be advantageous; the antimicrobial potency may be related to the inducibility of a helical conformation in a membrane-mimicking environment rather than to the intrinsic helical stability (37)(38)(39)47). The initial electrostatic interaction and the following hydrophobic partition provide AMPs with the unique ability to be highly water soluble but also to be able to interact strongly with negatively charged phospholipid bilayers (37)(38)(39)48).…”

Section: Discussionmentioning

confidence: 99%

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Structural Insights into and Activity Analysis of the Antimicrobial Peptide Myxinidin

Cantisani

Finamore

Mignogna

et al. 2014

Antimicrob Agents Chemother

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eThe marine environment has been poorly explored in terms of potential new molecules possessing antibacterial activity. Antimicrobial peptides (AMPs) offer a new potential class of pharmaceuticals; however, further optimization is needed if AMPs are to find broad use as antibiotics. We focused our studies on a peptide derived from the epidermal mucus of hagfish (Myxine glutinosa L.), which was previously characterized and showed high antimicrobial activity against human and fish pathogens. In the present work, the activities of myxinidin peptide analogues were analyzed with the aim of widening the original spectrum of action of myxinidin by suitable changes in the peptide primary structure. The analysis of key residues by alanine scanning allowed for the design of novel peptides with increased activity. We identified the amino acids that are of the utmost importance for the observed antimicrobial activities against a set of pathogens comprising both Gram-negative and Gram-positive bacteria. Overall, optimized bactericidal potency was achieved by adding a tryptophan residue at the N terminus and by the simultaneous substitution of residues present in positions 3, 4, and 11 with arginine. These results indicate that the myxinidin analogues emerge as an attractive alternative for treating drug-resistant infectious diseases and provide key insights into a rational design for novel agents against these pathogens.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Structural Insights into and Activity Analysis of the Antimicrobial Peptide Myxinidin

Cantisani

Finamore

Mignogna

et al. 2014

Antimicrob Agents Chemother

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“…Improved bactericidal potency (Malmsten et al 2011) Automatically designed peptide antibiotics (adepantins) . Based on anuran AMPs (Juretic´et al 2009) . (Giuliani and Rinaldi 2011) .…”

Section: Virusesmentioning

confidence: 99%

New trends in peptide-based anti-biofilm strategies: a review of recent achievements and bioinformatic approaches

2012

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Antimicrobial peptides (AMPs) have a broad spectrum of activity and unspecific mechanisms of action. Therefore, they are seen as valid alternatives to overcome clinically relevant biofilms and reduce the chance of acquired resistance. This paper reviews AMPs and anti-biofilm AMP-based strategies and discusses ongoing and future work. Recent studies report successful AMP-based prophylactic and therapeutic strategies, several databases catalogue AMP information and analysis tools, and novel bioinformatics tools are supporting AMP discovery and design. However, most AMP studies are performed with planktonic cultures, and most studies on sessile cells test AMPs on growing rather than mature biofilms. Promising preliminary synergistic studies have to be consubstantiated and the study of functionalized coatings with AMPs must be further explored. Standardized operating protocols, to enforce the repeatability and reproducibility of AMP anti-biofilm tests, and automated means of screening and processing the ever-expanding literature are still missing.

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Bioactive Synthetic Polymers

et al. 2021

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Progress in these arenas has been driven by the discovery of inert, biocompatible polymers to provide the desired function without eliciting undesirable responses from the host environment. While concerns regarding the fate of these materials have led to an ongoing hunt for bioresorbable materials, it is important to note that synthetic polymers have been reported to elicit a biological response on their own. [2j,5] While the biological response is often toxic in nature and therefore undesirable for many applications, it poses a question: can the intrinsic bioactivity of synthetic polymers be harnessed for therapeutic interventions? This idea of intrinsic bioactivity is distinct from the long history of work pertaining to the use of synthetic polymers within biomedical settings. Polymers have indeed been extensively explored and continue to be investigated as (nano)carriers facilitating the delivery of bioactive payloads; in the majority of cases, the (nano)carrier bereft of its cargo is presented to provide little to no effect, demonstrating its role as an ideal delivery vehicle. [6] Polymers with intrinsic bioactivity diverge from this well-known concept by inducing biological change (i.e., bioactivity) by themselves in the absence of any conjugated or encapsulated species. [7] Interestingly, this previously posed question generated significant interest prior to the advent of drug-delivery approaches. [8] Among these early studies, a synthetic polymer, designated DIVEMA, garnered significant attention for its presentation of an outstanding breadth of bioactivity. [9] DIVEMA is a copolymer of divinyl ether (DVE) and maleic anhydride (MA) in a 1:2 ratio, with its proposed cyclopolymerization mechanism affording an in-chain pyran which consequently caused it to be more prominently known as Pyran copolymer. A hydrolyzed and neutralized version received the designation NSC 46015 and was approved for experimental clinical evaluation due to its antitumor activity against several cancers, including Adenocarcinoma 755, Lewis lung carcinoma, and Dunning ascites leukemia. [10] Moreover, its ability to induce interferon expression led to its evaluation against several viruses and reports of prophylactic action in murine models. DIVEMA has also demon strated antimicrobial activity against both Grampositive and Gram-negative bacteria and fungi. Despite this wide-ranging bioactivity, DIVEMA also presented a number of toxic side effects, the summation of which was not favorable for clinical use. Such side effects were common to many of the investigated synthetic polymers of the time and their failure in clinical trials is reflected in an absence of such therapeutic interventions as approved medicines.Synthetic polymers are omnipresent in society as textiles and packaging materials, in construction and medicine, among many other important applications. Alternatively, natural polymers play a crucial role in sustaining life and allowing organisms to adapt to their environments by performing key biological functions such as m...

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Computational Design of Highly Selective Antimicrobial Peptides

Cited by 79 publications

References 34 publications

Structural Insights into and Activity Analysis of the Antimicrobial Peptide Myxinidin

Structural Insights into and Activity Analysis of the Antimicrobial Peptide Myxinidin

New trends in peptide-based anti-biofilm strategies: a review of recent achievements and bioinformatic approaches

Bioactive Synthetic Polymers

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