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Oligopeptides stand out for their remarkable structural variability, ease of synthesis, and amenability to functionalization, making them exceedingly appealing for crafting functional nanostructured materials. The low metabolic stability of natural peptides can be overcome by replacing α-amino acids with β3- amino acids, to yield artificial peptides best described as substituted β3-oligoamides. Controlling the morphology of such structures by varying the amino acid residues and altering the oligoamide termini makes it possible to adapt the core design to a range of hierarchical structures and function. Conductivity is a desired property in such nanomaterials; preferably conductive materials should be chemically anchored to a highly conductive metal, such as gold surface to connect to macroscopic electronics. It is preferable to use thiol functionality, however β3 cysteine is not synthetically achieveable. In this study β3 [SLIA] oligoamide has been synthesized and functionalized at the N terminus with a thiol moiety. After successful synthesis and purification, the thiolated oligoamide was physically characterized to confirm binding to gold, self-assembly and hetero assembly on these anchor points. It was demonstrated with a quartz crystal microbalance (QCM) that self-assembling monolayers can be formed on a gold surface and the formation of a S-Au bond was confirmed with X-ray photoelectron spectroscopy. Growth of Ac-β3[WKLWEL] fibres on these anchor points was confirmed by using atomic force microscopy and QCM. Hence, a viable metal anchor has been established that lays the foundations for the future development of molecular electronics based on β3 oligoamides.

Antimicrobial resistance (AMR) poses a serious threat to human health worldwide. It is now more challenging than ever to introduce a potent antibiotic to the market considering rapid emergence of antimicrobial resistance, surpassing the rate of antibiotic drug discovery. Hence, new approaches need to be developed to accelerate the rate of drug discovery process and meet the demands for new antibiotics, while reducing the cost of their development. Machine learning holds immense promise of becoming a useful tool, especially since in the last two decades, exponential growth has occurred in computational power and biological big data analytics. Recent advancements in machine learning algorithms for drug discovery have provided significant clues for potential antibiotic classes. Apart from discovery of new scaffolds, the machine learning protocols will significantly impact prediction of AMR patterns and drug metabolism. In this review, we outline power of machine learning in antibiotic drug discovery, metabolic fate, and AMR prediction to support researchers engaged and interested in this field. [ABSTRACT FROM AUTHOR]

The properties of self-assembled phospholipid membranes are of essential importance in biochemistry and physical chemistry, providing a platform for many cellular life functions. Far-infrared (far-IR) vibrational spectroscopy, on the other hand, is a highly information-rich method to characterize intermolecular interactions and collective behaviour of lipids that can help explain, e.g., chain packing, thermodynamic phase behaviour, and sequestration. However, reliable interpretation of the far-IR spectra is still lacking. Here we present a molecular dynamics (MD) based approach to simulate vibrational modes of individual lipids and in an ensemble. The results are a good match to synchrotron far-IR measurements and enable identification of the molecular motions corresponding to each vibrational mode, thus allowing the correct interpretation of membrane spectra with high accuracy and resolving the longstanding ambiguities in the literature in this regard. Our results demonstrate the feasibility of using MD simulations for interpreting far-IR spectra broadly, opening new avenues for practical use of this powerful method. [ABSTRACT FROM AUTHOR]

Oligopeptides stand out for their remarkable structural variability, ease of synthesis, and amenability to functionalization, making them exceedingly appealing for crafting functional nanostructured materials. The low metabolic stability of natural peptides can be overcome by replacing α-amino acids with β3- amino acids, to yield artificial peptides best described as substituted β3-oligoamides. Controlling the morphology of such structures by varying the amino acid residues and altering the oligoamide termini makes it possible to adapt the core design to a range of hierarchical structures and function. Conductivity is a desired property in such nanomaterials; preferably conductive materials should be chemically anchored to a highly conductive metal, such as gold surface to connect to macroscopic electronics. It is preferable to use thiol functionality, however β3 cysteine is not synthetically achieveable. In this study β3 [SLIA] oligoamide has been synthesized and functionalized at the N terminus with a thiol moiety. After successful synthesis and purification, the thiolated oligoamide was physically characterized to confirm binding to gold, self-assembly and hetero assembly on these anchor points. It was demonstrated with a quartz crystal microbalance (QCM) that self-assembling monolayers can be formed on a gold surface and the formation of a S-Au bond was confirmed with X-ray photoelectron spectroscopy. Growth of Ac-β3[WKLWEL] fibres on these anchor points was confirmed by using atomic force microscopy and QCM. Hence, a viable metal anchor has been established that lays the foundations for the future development of molecular electronics based on β3 oligoamides. [ABSTRACT FROM AUTHOR]

C-terminal amidation is a common feature of wild type membrane disrupting antimicrobial peptides (AMPs). Empirical evidence suggests that this modification increases antimicrobial efficacy. However, the actual role of C-terminal amidation in the molecular mechanism of action of AMPs is not fully understood. Amidation alters two key properties simultaneously: the net charge and helicity of the peptide, both of which are implicated in the mechanism of action. However, the differences between the physicochemical properties of the carboxyl and amide moieties have been disregarded in former studies. In this study we assessed whether the difference in activity is only caused by changes in the helicity and overall charge of a peptide, i.e. whether the chemistry of the terminus is otherwise irrelevant. To do so, the membrane disrupting activity of a modified aurein 1.2 peptide was studied in which a secondary amide was formed with a terminal methyl group, instead of the primary amide as in the wild type peptide. Results of quartz crystal microbalance, dye leakage and circular dichroism experiments show that the activity of the modified peptide is substantially reduced compared to the wild type peptide, in particular that the modified peptide exhibited a much-reduced ability to bind to the membrane. Thus, the primary amide at the C-terminus is required to bind to the membrane, and a secondary amide cannot serve the same purpose. We hypothesize that this difference is related to the hydration state of the terminus. The lack of membrane binding ability of the modified peptide identifies the primary amide moiety at the C terminus as a specific membrane binding motif.

Preventing the corrosion of iron in inaccessible structures requires a coating method that reaches all surface areas and creates a uniform protective layer. An ages old practice to protect iron artefacts is to coat them with animal fat, that is, a mixture of lipids. This “method” is accidentally ingenious: some natural phospholipids found in animal fat have the potential to form a tightly packed self-assembled monolayer on metal oxide surfaces, similar to the surfactant monolayers that have attracted increasing attention lately. Thus, the most primitive corrosion prevention method may point at a way to coat complex iron structures in an industrial environment. Here the ability of phosphatidic acid, a natural lipid, to coat and protect iron surfaces was examined. Iron coated quartz crystal microbalance (QCM) sensors were used for the experiments, to monitor the deposition of the lipid as well as the acidic corrosion (dissolution) of iron in situ, in real time. The sensors were coated by self-assembled monolayers of di-myristoyl phosphatidic acid using the liposome deposition method. In this process, 50-100 nm vesicles formed by the lipid are delivered in an aqueous solution and spontaneously coat the iron surfaces upon contact. QCM and ellipsometry measurements confirmed that continuous bilayer and monolayer surface coatings can be achieved by this method. QCM measurements also confirmed that the layers were corrosion resistant in 0.01M acetic acid solution that would dissolve the thin iron layer in minutes in the absence of the protective coating. XPS results suggested a chemisorption-based mechanism of phosphatidic acid attachment to the iron surface. Hence, liposome deposition of phosphatidic acid offers a suitable solution to coat iron surfaces in inaccessible structures in situ.

Glucoraphanin is one of the best known glucosinolates because of its health benefits. The compound is known to eliminate carcinogens in tissue and hence is frequently studied for its cancer preventative properties. In this work, the total synthesis of α- and β-glucoraphanin epimers was attempted. β-Glucoraphanin potassium salt was successfully synthesized in high overall yield, whereas the α-epimer was found to be unstable as it decomposed in the final step of the total synthesis. The anti-inflammatory activity of the synthetic glucoraphanin was determined by inhibition of the release of tumor necrosis factor alpha (TNF-α) secretion in lipopolysaccharide-stimulated THP-1 cells. It was shown that in the presence of either the synthetic or natural glucoraphanin, TNF-α secretion was significantly reduced (≈52 % inhibition) at a concentration of 15 μM.

Novel tetrahydrofuran lignans (HFL) identified from Anogeissus rivularis showed potential antioxidant effects in previous studies, increasing the possibility of modifying these substances for medicinal use in illnesses associated with oxidative stress. A detailed analysis of the antioxidant activity of these compounds is therefore beneficial for medical uses. The capability of four HFL variants to scavenge radicals in polar (water at pH = 7.40) and nonpolar (gas phase and pentyl ethanoate) media was examined in this work employing kinetic and thermodynamic models. The hydroperoxyl radical trapping activity of HFL with the overall rate constants of 105–107 M−1 s−1 is faster in polar than in nonpolar media. In nonpolar environments, the FHT pathway is primarily responsible for the activity of these HFL; however, in the aqueous solution, the SET pathway is favored. According to the computed data, the hydroperoxyl radical trapping activity of HFL in the studied environments follows the order 2 > 3 ∼ 4 > 1. In particular, the scavenging of HOO˙ radicals by compound 2 is roughly 16 and 100 times greater in lipid and aqueous media, respectively, than the activity of Trolox in the same. Considering a parallel antioxidant pathway via inhibiting free radical producing enzymes, docking analysis revealed that the investigated compounds also have a strong affinity for the CP450, MP, and NO enzymes, exhibiting favorable interactions with key amino acid residues. Thus tetrahydrofuran lignan 2 is a promising natural antioxidant in physiological environments. [ABSTRACT FROM AUTHOR]