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Peptides have attracted great interest as platforms for the design of nanocomposite hydrogels due to their distinct bioactivity, biofunctionality and biocompatibility. Previously, we have reported on a family of peptides that self‐assembled to form stabilised three‐dimensional hydrogel networks, displaying potent antimicrobial activity. In this paper, we report on the use of these hydrogelator sequences and their analogues as stabilisers and growth controllers to synthesise anisotropic gold nanoparticles (AuNPs) of different sizes and shapes. In particular, hollow spherical nanoparticles were obtained for HG2.81‐AuNPs, whereas hexagonal nanoparticles were observed for TOH_1N‐AuNPs and PentaOH‐AuNPs in their respective hydrogel networks. The PentaOH‐AuNPs' hydrogel exhibited excellent results with high antimicrobial potency against Staphylococcus aureus and Pseudomonas aeruginosa ATCC 27853 and negligible cytotoxicity. On the other hand, TOH_1N‐AuNPs showed no antibacterial activity and no cytotoxicity, demonstrating the versatility of these peptides. This work gives credence towards the development of these materials towards further applications such as in tissue culture technology and wound dressing materials. [ABSTRACT FROM AUTHOR]

Phytophthora species are a genus in the oomycete class and are destructive plant pathogens. The ability to inhibit all stages in the life cycle of these aggressive Phytophthora pathogens is essential for the long‐term protection of native trees, plantation forests and horticultural crops that they threaten. Compounds having this ability are currently scarce. In this study, antifungal compounds of natural and synthetic origin were screened against the mycelial, zoospore and oospore life stages of Phytophthora agathidicida (P. agathidicida 18406), P. multivora (P. multivora 20280) and P. cinnamomi (P. cinnamomi 20276, 3910 and 21050). An antifungal lipopeptide showed promising (25–200 μg/mL) antimycelial activity against all the tested Phytophthora species, rapid (c. 30 s) inhibition of P. agathidicida, P. multivora and P. cinnamomi 3910 zoospore motility, inhibition of zoospore germination at 12.5–50 μg/mL and reduced the viability of P. agathidicida and P. multivora oospores at 1000 μg/mL. Polygodial extracted from New Zealand horopito leaves showed more potent (5–50 μg/mL) antimycelial activity and inhibited zoospore motility of P. agathidicida, P. multivora and P. cinnamomi 3910, although at a slightly slower rate; however, it was inactive against oospores. Polygodial and lipopeptide protected kauri and avocado leaves from Phytophthora infection and did not show symptoms of phytotoxicity. Polygodial also inhibited the growth of P. agathidicida in soil. This study demonstrates for the first time the promising antioomycete potential of compounds ranging from small molecule natural products to larger biomolecules such as lipopeptides, which can be developed as compounds to deactivate the different life stages of aggressive Phytophthora species. [ABSTRACT FROM AUTHOR]

A safer method for the synthesis of the sulfonamide drug sulfathiazole, for undergraduate classes, is described. This method improves upon procedures currently followed in several undergraduate teaching laboratories for the synthesis of sulfathiazole. Key features of this procedure include the total exclusion of pyridine, which has potential health hazards, from the first step of the synthesis and a simplified procedure for converting the intermediate p-acetamidobenzenesulfonamide to the final product by acid hydrolysis. Characterization of the synthetic sulfathiazole obtained by the modified route was achieved using MS, NMR, and antibacterial activity testing of the synthetic product against "Escherichia coli" DH5[alpha]. (Contains 2 tables and 2 schemes.)

Cheap artificial light harvesting systems, which competently harvest solar energy and promote efficient energy transfer, are highly sought after in the renewable sector. We report the synthesis of self‐assembled peptide‐porphyrin fibers (SJ 6) fabricated with iron(III) oxide (Fe3O4) nanoparticles as feasible electron acceptors. Charge‐complementarity between the negatively charged peptide (20E) and the protonated Zn‐tetraphenyl porphyrin (ZnTPyP) led to an ordered assembly of the ZnTPyP molecules, enabling efficient light harvesting. X‐ray diffraction data indicates a more ordered structure in SJ 6 compared to 20E and ZnTPyP. The incorporation of Fe3O4 nanoparticles into SJ 6 showed significant fluorescence quenching, indicating efficient electron flow from the donor to the acceptor. The SJ 6‐nFe3O4 system performed the light reaction of photosynthesis as confirmed by the reduction of 1 mM NAD+ to 0.180 mM NADH upon exposure to visible light (Xe lamp λ > 420 nm) for 1 h. The photochemical regeneration of NADH using the SJ 6‐nFe3O4 system was coupled to glutamate dehydrogenase‐catalyzed conversion of α‐ketoglutarate to L‐glutamate. These results confirm the successful synthesis of an artificial light harvesting peptide‐porphyrin system with Fe3O4 nanoparticles as promising low‐cost electron separators. [ABSTRACT FROM AUTHOR]

Targeting amyloidosis requires high-resolution insight into the underlying mechanisms of amyloid aggregation. The sequence-specific intrinsic properties of a peptide or protein largely govern the amyloidogenic propensity. Thus, it is essential to delineate the structural motifs that define the subsequent downstream amyloidogenic cascade of events. Additionally, it is important to understand the role played by extrinsic factors, such as temperature or sample agitation, in modulating the overall energy barrier that prompts divergent nucleation events. Consequently, these changes can affect the fibrillation kinetics, resulting in structurally and functionally distinct amyloidogenic conformers associated with disease pathogenesis. Here, we have focused on human Islet Polypeptide (hIAPP) amyloidogenesis for the full-length peptide along with its N- and C-terminal fragments, under different temperatures and sample agitation conditions. This helped us to gain a comprehensive understanding of the intrinsic role of specific functional epitopes in the primary structure of the peptide that regulates amyloidogenesis and subsequent cytotoxicity. Intriguingly, our study involving an array of biophysical experiments and ex vivo data suggests a direct influence of external changes on the C-terminal fibrillating sequence. Furthermore, the observations indicate a possible collaborative role of this segment in nucleating hIAPP amyloidogenesis in a physiological scenario, thus making it a potential target for future therapeutic interventions. [ABSTRACT FROM AUTHOR]

The effect on secondary structure and antimicrobial activity of introducing different cyclic constraints in linear β‐hairpin antimicrobial peptides has been investigated with the intention of generating cyclic β sheets as promising antimicrobials with improved therapeutic potential. The linear peptides were cyclized head to tail either directly or after the addition of either a second turn motif or a disulfide bridge. The propensity of these peptides to adopt a cyclic β‐sheet structure has been correlated to their antibacterial activity. All cyclic peptides showed enhanced activity, compared with their linear counterparts against methicillin‐resistant Staphylococcus aureus. Scanning electron microscopy and transmission electron microscopy studies showed that this family kills bacteria through membrane lysis. The peptide that showed the best efficacy against all strains (exhibiting nanomolar activity), while retaining low haemolysis, bears two symmetrical, homochiral d‐phe‐2‐Abz‐d‐ala turns and adopted a flexible structure. Its twin peptide that bears heterochiral turns (one with d‐ala and one with L‐Ala) showed reduced antibacterial activity and higher percentage of haemolysis. Circular dichroism and nuclear magnetic resonance spectroscopy indicate that heterochirality in the two turns leads to oligomerization of the peptide at higher concentrations, stabilizing the β‐sheet secondary structure. More rigid secondary structure is associated with lower activity against bacteria and loss of selectivity. [ABSTRACT FROM AUTHOR]

The combination of more than one bioactive moiety in a multitargeted anticancer agent may result in synergistic activity of its components. Using this concept, bioorganometallic compounds were designed to feature a metal center, a 2‐pyridinecarbothioamide (PCA), and a hydroxamic acid, which is found in the anticancer drug vorinostat (SAHA). The organometallics showed inhibitory activity in the nanomolar range against histone deacetylases (HDACs) as the key target for SAHA. In particular, the Rh complex was a potent inhibitor of HDAC6 over HDAC1 and HDAC8. Whereas this complex was highly cytotoxic in human cancer cells, it showed low toxicity in hemolysis studies and zebrafish, demonstrating the role of the metal center. For this complex a slightly reduced expression of vascular endothelial growth factor receptor 2 (VEGFR2) was established, which was upregulated by SAHA. This finding indicates that the new organometallics display different modes of action than their bioactive components. [ABSTRACT FROM AUTHOR]

An investigation using recombinant ribosomal proteins and synthetic peptide models was conducted to uncover the effect of the introduction of a negative charge at the C-terminal tail of ribosomal protein S15. Our results help provide a chemical rationale towards understanding how G2019S LRRK2, a common clinical mutation, causes Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: Povidone-iodine is used as a cost-effective broad-spectrum antiseptic in the prophylaxis and treatment of certain ocular infections. In this study, the stability, ophthalmic irritation potential and antibacterial efficacy of an extemporaneous povidone-iodine preparation was determined using established ex vivo and in vitro assays.Methods: Extemporaneous iodine was prepared by simple dilution in normal saline. Preparation stability was evaluated by monitoring concentration and pH. Ocular safety was determined using the bovine cornea opacity and permeability assay. Efficacy was assessed by determining the minimum inhibitory and minimum bactericidal concentration of the preparation on Staphylococcus aureus and Pseudomonas aeruginosa.Results: Diluted povidone-iodine maintained its stability over the 28-day evaluation. The formulation caused mild ocular irritation at the lowest prepared concentration (0.5 per cent w/v), with irritation noticeably increased at higher concentrations. The preparation showed minimum bactericidal and inhibitory concentrations of 0.078 and 0.3 per cent w/v on S. aureus and P. aeruginosa, respectively.Conclusions: This study confirms the stability and broad-spectrum antibacterial efficacy of povidone-iodine, while addressing the ocular irritation potential of this chemical. [ABSTRACT FROM AUTHOR]

Redox-modulating anticancer drugs allow the exploitation of altered redox biology observed in many cancer cells. We discovered dinuclear RhIII(Cp*) and IrIII(Cp*) complexes that have in vitro anticancer activity superior to cisplatin and the investigational drug IT-139, while being less toxic in haemolysis and in vivo zebrafish models. The mode of action appears to be related to DNA damage and ROS-mediated stress pathways. [ABSTRACT FROM AUTHOR]

To date, the synthesis of peptides is concurrent with the production of enormous amounts of toxic waste. DMF, CH2Cl2, and NMP are three of the most toxic organic solvents used in chemical synthesis and are the most common solvents used for peptide synthesis. Additionally, concerns about the hepatotoxicity caused by exposure to DMF and from the toxic and allergenic nature of additives used in peptide synthesis necessitates the need for a green, environmentally friendly, and safer protocol for peptide synthesis. This review summarizes the current literature on green solid‐phase peptide synthesis successes and challenges encountered. The review concludes with suggestions for future research towards a simple and efficient green peptide synthesis protocol. [ABSTRACT FROM AUTHOR]

Three linear peptides incorporating d‐Phe‐2‐Abz as the turn motif are reported. Peptide 1, a hydrophobic β‐hairpin, served as a proof of principle for the design strategy with both NMR and CD spectra strongly suggesting a β‐hairpin conformation. Peptides 2 and 3, designed as amphipathic antimicrobials, exhibited broad spectrum antimicrobial activity, with potency in the nanomolar range against Staphylococcus aureus. Both compounds possess a high degree of selectivity, proving non‐haemolytic at concentrations 500 to 800 times higher than their respective minimal inhibitory concentrations (MICs) against S. aureus. Peptide 2 induced cell membrane and cell wall disintegration in both S. aureus and Pseudomonas aeruginosa as observed by transmission electron microscopy. Peptide 2 also demonstrated moderate antifungal activity against Candida albicans with an MIC of 50 μM. Synergism was observed with sub‐MIC levels of amphotericin B (AmB), leading to nanomolar MICs against C. albicans for peptide 2. Based on circular dichroism spectra, both peptides 2 and 3 appear to exist as a mixture of conformers with the β‐hairpin as a minor conformer in aqueous solution, and a slight increase in hairpin population in 50% trifluoroethanol, which was more pronounced for peptide 3. NMR spectra of peptide 2 in a 1:1 CD3CN/H2O mixture and 30 mM deuterated sodium dodecyl sulfate showed evidence of an extended backbone conformation of the β‐strand residues. However, inter‐strand rotating frame Overhauser effects (ROE) could not be detected and a loosely defined divergent hairpin structure resulted from ROE structure calculation in CD3CN/H2O. The loosely defined hairpin conformation is most likely a result of the electrostatic repulsions between cationic strand residues which also probably contribute towards maintaining low haemolytic activity. [ABSTRACT FROM AUTHOR]

Abstract: This work demonstrates that the human autophagy 16 polypeptide (Atg16) has antibacterial and antibiofilm potential, perturbs both Gram positive and negative bacterial membranes and subsequently also produces ROS in compromised bacteria. Engineered Atg 16 analogues containing 1‐ and 2‐naphthyl alanines showed significant enhancement of antibacterial activity and eradicated biofilms while also possessing negligible hemolysis of mouse erythrocytes. This new family of antibacterial peptides are promising candidates in the fight against bacterial biofilms, responsible for several thousand deaths annually which are predicted to rise into the millions. [ABSTRACT FROM AUTHOR]

Herein we report the unique conformations adopted by linear and cyclic tetrapeptides (CTPs) containing 2-aminobenzoic acid (2-Abz) in solution and as single crystals. The crystal structure of the linear tetrapeptide H2N- d-Leu- d-Phe-2-Abz- d-Ala-COOH ( 1) reveals a novel planar peptidomimetic β-turn stabilized by three hydrogen bonds and is in agreement with its NMR structure in solution. While CTPs are often synthetically inaccessible or cyclize in poor yield, both 1 and its N-Me- d-Phe analogue ( 2) adopt pseudo-cyclic frameworks enabling near quantitative conversion to the corresponding CTPs 3 and 4. The crystal structure of the N-methylated peptide ( 4) is the first reported for a CTP containing 2-Abz and reveals a distinctly planar 13-membered ring, which is also evident in solution. The N-methylation of d-Phe results in a peptide bond inversion compared to the conformation of 3 in solution. [ABSTRACT FROM AUTHOR]

Archaea was until recently considered as a third domain of life in addition to bacteria and eukarya but recent studies support the existence of only two superphyla (bacteria and archaea). The fundamental differences between archaeal, bacterial, and eukaryal cells are probably the main reasons for the comparatively lower susceptibility of archaeal strains to current antimicrobial agents. The possible emerging pathogenicity of archaea and the role of archaeal methanogens in methane emissions, a potent greenhouse gas, has led many researchers to examine the sensitivity patterns of archaea and make attempts to find agents that have significant anti-archaeal activity. Even though antimicrobial peptides (AMPs) are well known with several published reviews concerning their mode of action against bacteria and eukarya, to our knowledge, to date no reviews are available that focus on the action of these peptides against archaea. Herein, we present a review on all the peptides that have been tested against archaea. In addition, in an attempt to shed more light on possible future work that needs to be performed we have included a brief overview of the chemical characteristics, spectrum of activity, and the known mechanism of action of each of these peptides against bacteria and/or fungi. We also discuss the nature of and key physiological differences between Archaea, Bacteria, and Eukarya that are relevant to the development of anti-archaeal peptides. Despite our relatively limited knowledge about archaea, available data suggest that AMPs have an even broader spectrum of activity than currently recognized. [ABSTRACT FROM AUTHOR]

Antifreeze proteins modify the growth of ice crystals. We present a rational approach towards the design of short peptide analogues of the 8.7 kDa disulfide-bridged β-helical hyperactive insect antifreeze protein. Our synthetic peptides bind and modify the shape of ice crystals, and show enhanced antifreeze activity with the addition of citrate. [ABSTRACT FROM AUTHOR]