Synergy between the clavanins as a weapon against multidrug-resistant .

Finding new antibiotics that can act synergistically with each other offers many benefits such as lower dosages used for each drug, improved pathogen clearance, and ability to act against multi-drug resistant strains. In this study, six peptides isolated from the tunicate were evaluated for their synergistic interaction using the checkerboard assay and the time kill kinetics assay. Using two different tests, we report synergy between clavanin D and clavaspirin in both tests and synergy between clavanin A and B only in the checkerboard test when used against the multidrug resistant 0136.

1,2-Azolylamidino ruthenium(II) complexes with DMSO ligands: electro- and photocatalysts for CO reduction.

New 1,2-azolylamidino complexes -[RuCl(DMSO)(NHC(R)az*-κN,N)]OTf [R = Me (2), Ph (3); az* = pz (pyrazolyl, a), indz (indazolyl, b)] are synthesized chloride abstraction from their corresponding precursors ,-[RuCl(DMSO)(az*H)] (1) after subsequent base-catalyzed coupling of the appropriate nitrile with the 1,2-azole previously coordinated. All the compounds are characterized by H NMR, C NMR and IR spectroscopy. Those derived from MeCN are also characterized by X-ray diffraction.

The Synergy between Zinc and Antimicrobial Peptides: An Insight into Unique Bioinorganic Interactions.

Antimicrobial peptides (AMPs) are essential components of innate immunity across all species. AMPs have become the focus of attention in recent years, as scientists are addressing antibiotic resistance, a public health crisis that has reached epidemic proportions. This family of peptides represents a promising alternative to current antibiotics due to their broad-spectrum antimicrobial activity and tendency to avoid resistance development.

Synthesis and Characterization of Preacinetobactin and 5-Phenyl Preacinetobactin.

We report the first total synthesis of 5-phenyl preacinetobactin and its characterization. The route was developed for the synthesis of preacinetobactin, the siderophore critical to the Gram-negative pathogen . It leverages a C5-substituted benzaldehyde as a key starting material and should enable the synthesis of similar analogs.

Exploring synergy and its role in antimicrobial peptide biology.

Antimicrobial peptides will be an essential component in combating the escalating issue of antibiotic resistance. Identifying synergistic combinations of two or more substances will increase the value of these peptides further. Several potential pitfalls in conducting synergy testing with peptides are discussed in detail.

Copper-binding anticancer peptides from the piscidin family: an expanded mechanism that encompasses physical and chemical bilayer disruption.

In the search for novel broad-spectrum therapeutics to fight chronic infections, inflammation, and cancer, host defense peptides (HDPs) have garnered increasing interest. Characterizing their biologically-active conformations and minimum motifs for function represents a requisite step to developing them into efficacious and safe therapeutics. Here, we demonstrate that metallating HDPs with Cu is an effective chemical strategy to improve their cytotoxicity on cancer cells.

Antimicrobial Susceptibility Testing of Antimicrobial Peptides Requires New and Standardized Testing Structures.

The need for optimized as well as standardized test systems of novel antimicrobial peptides (AMPs) was discussed by experts in the field at the International Meeting on Antimicrobial Peptides (IMAP) 2017 and the 2019 Gordon Research Conference (GRC) on Antimicrobial Peptides, and a survey related to this topic was circulated to participants to collate opinions. The survey included questions ranging from the relevance of susceptibility testing for understanding the mode of action of AMPs, to the importance of optimization and a degree of standardization of test methods and their clinical relevance. Based on the survey results, suggestions for future improvements in the research field are made.

β-Oxochlorin cobalt(II) complexes catalyze the electrochemical reduction of CO.

Inspired by the architecture of the macrocycle of heme d1, a series of synthetic mono-, di- and tri-β-oxo-substituted porphyrinoid cobalt(ii) complexes were evaluated as electrocatalytic CO2 reducers, identifying complexes of unusually high efficiencies in generating multi-electron reduction products, including CH4.

Unraveling the implications of multiple histidine residues in the potent antimicrobial peptide Gaduscidin-1.

The development of antimicrobial peptides (AMPs) as potential therapeutics requires resolving the foundational principles behind their structure-activity relationships. The role of histidine residues within AMPs remains a mystery despite the fact that several potent peptides containing this amino acid are being considered for further clinical development. Gaduscidin-1 (Gad-1) is a potent AMP from Atlantic cod fish that has a total of five His residues.

Methane Generation from CO with a Molecular Rhenium Catalyst.

The atomic-level tunability of molecular structures is a compelling reason to develop homogeneous catalysts for challenging reactions such as the electrochemical reduction of carbon dioxide to valuable C-C products. Of particular interest is methane, the largest component of natural gas. Herein, we report a series of three isomeric rhenium tricarbonyl complexes coordinated by the asymmetric diimine ligands 2-(isoquinolin-1-yl)-4,5-dihydrooxazole (), 2-(quinolin-2-yl)-4,5-dihydrooxazole (), and 2-(isoquinolin-3-yl)-4,5-dihydrooxazole () that catalyze the reduction of CO to carbon monoxide and methane, albeit the latter with a low efficiency.

Antimicrobial Peptides and Copper(II) Ions: Novel Therapeutic Opportunities.

The emergence of new pathogens and multidrug resistant bacteria is an important public health issue that requires the development of novel classes of antibiotics. Antimicrobial peptides (AMPs) are a promising platform with great potential for the identification of new lead compounds that can combat the aforementioned pathogens due to their broad-spectrum antimicrobial activity and relatively low rate of resistance emergence. AMPs of multicellular organisms made their debut four decades ago thanks to ingenious researchers who asked simple questions about the resistance to bacterial infections of insects.

The Antimicrobial Peptide Gad-1 Clears Pseudomonas aeruginosa Biofilms under Cystic Fibrosis Conditions.

Bacterial infections in cystic fibrosis (CF) patients are an emerging health issue and lead to a premature death. CF is a hereditary disease that creates a thick mucus in the lungs that is prone to bacterial biofilm formation, specifically Pseudomonas aeruginosa biofilms. These biofilms are very difficult to treat because many of them have antibiotic resistance that is worsened by the presence of extracellular DNA (eDNA).

(1,2-Azole)bis(bipyridyl)ruthenium(II) Complexes: Electrochemistry, Luminescent Properties, And Electro- And Photocatalysts for CO Reduction.

New -(1,2-azole)-aquo bis(2,2'-bipyridyl)ruthenium(II) (1,2-azole (az*H) = pzH (pyrazole), dmpzH (3,5-dimethylpyrazole), and indzH (indazole)) complexes are synthesized via chlorido abstraction from -[Ru(bipy)Cl(az*H)]OTf. The latter are obtained from -[Ru(bipy)Cl] after the subsequent coordination of the 1,2-azole. All the compounds are characterized by H, C, N NMR spectroscopy as well as IR spectroscopy.

Peptide-Ruthenium Conjugate as an Efficient Photosensitizer for the Inactivation of Multidrug-Resistant Bacteria.

Antimicrobial photodynamic therapy (APDT) has gained increased attention because of its broad spectrum activity and lower likelihood to elicit bacterial resistance. Although many photosensitizers excel at eradicating Gram-positive bacterial infections, they are generally less potent when utilized against Gram-negative bacteria. We hypothesized that conjugating the DNA-targeting, antimicrobial peptide buforin II to a metal-based photosensitizer would result in a potent APDT agent.

Antimicrobial Susceptibility Testing of Antimicrobial Peptides to Better Predict Efficacy.

During the development of antimicrobial peptides (AMP) as potential therapeutics, antimicrobial susceptibility testing (AST) stands as an essential part of the process in identification and optimisation of candidate AMP. Standard methods for AST, developed almost 60 years ago for testing conventional antibiotics, are not necessarily fit for purpose when it comes to determining the susceptibility of microorganisms to AMP. Without careful consideration of the parameters comprising AST there is a risk of failing to identify novel antimicrobials at a time when antimicrobial resistance (AMR) is leading the planet toward a post-antibiotic era.

A Potent Host Defense Peptide Triggers DNA Damage and Is Active against Multidrug-Resistant Gram-Negative Pathogens.

Gram-negative bacteria are some of the biggest threats to public health due to a large prevalence of antibiotic resistance. The difficulty in treating bacterial infections, stemming from their double membrane structure combined with efflux pumps in the outer membrane, has resulted in a much greater need for antimicrobials with activity against these pathogens. Tunicate host defense peptide (HDP), Clavanin A, is capable of not only inhibiting Gram-negative growth but also potentiating activity in the presence of Zn(II).

Antimicrobial and Antibiofilm Activities of Helical Antimicrobial Peptide Sequences Incorporating Metal-Binding Motifs.

Antimicrobial peptides (AMPs) represent alternative strategies to combat the global health problem of antibiotic resistance. However, naturally occurring AMPs are generally not sufficiently active for use as antibiotics. Optimized synthetic versions incorporating additional design principles are needed.

Molecular Dynamics Investigation into the Effect of Zinc(II) on the Structure and Membrane Interactions of the Antimicrobial Peptide Clavanin A.

Clavanin A (ClavA) is an antimicrobial peptide (AMP) whose antimicrobial activity is enhanced in the presence of Zn(II) ions. The antimicrobial activity of ClavA has been shown to increase 16-fold in the presence of Zn(II) ions. In this study, we investigate the potential sources of this enhancement, namely, the effect of Zn(II) binding on the helical conformation of ClavA and on the ClavA interaction with a model for gram-negative bacterial membranes.

Synthetic Polymers To Promote Cooperative Cu Activity for O Activation: Poly vs Mono.

We report polymer-promoted cooperative catalysis of Cu for oxygen activation. A series of random copolymers containing dipicolylamine as binding motifs are designed to coordinate type-3 Cu sites. The Cu-copolymers show a 6-8-fold activity enhancement, compared to the molecular complex of Cu with an identical coordination site.

Direct oxygen isotope effect identifies the rate-determining step of electrocatalytic OER at an oxidic surface.

Understanding the mechanism of water oxidation to dioxygen represents the bottleneck towards the design of efficient energy storage schemes based on water splitting. The investigation of kinetic isotope effects has long been established for mechanistic studies of various such reactions. However, so far natural isotope abundance determination of O produced at solid electrode surfaces has not been applied.

Phagosomal Copper-Promoted Oxidative Attack on Intracellular Mycobacterium tuberculosis.

Copper (Cu) ions are critical in controlling bacterial infections, and successful pathogens like Mycobacterium tuberculosis (Mtb) possess multiple Cu resistance mechanisms. We report, as proof of concept, that a novel Cu hypersensitivity phenotype can be generated in mycobacteria, including Mtb, through a peptide, DAB-10, that is able to form reactive oxygen species (ROS) following Cu-binding. DAB-10 induces intramycobacterial oxidative stress in a Cu-dependent manner in vitro and during infection.

[Ru(tpy)(bpy)Cl]-Catalyzed reduction of carbon dioxide. Mechanistic insights by carbon-13 kinetic isotope effects.

In this work, we examine the use of competitive 13C kinetic isotope effects (13C KIEs) on CO2 reduction reactions that produce CO and formic acid as a means to formulate reaction mechanisms. The findings reported here mark a further advancement in the combined 13C KIE measurements and theoretical calculations methodology for probing CO2 conversion reactions.

Nuclease activity gives an edge to host-defense peptide piscidin 3 over piscidin 1, rendering it more effective against persisters and biofilms.

Host-defense peptides (HDPs) feature evolution-tested potency against life-threatening pathogens. While piscidin 1 (p1) and piscidin 3 (p3) are homologous and potent fish HDPs, only p1 is strongly membranolytic. Here, we hypothesize that another mechanism imparts p3 strong potency.