Host-Guest Interactions Facilitated by Chalcogen Bonding within Selenadiazole Functionalised Porphyrin Nanotubes.

The structural rigidity of tetrakis(4-pyridyl)porphyrin (TPyP) has been utilised to prepare a robust novel porous coordination polymer of composition Cd(TPyP)(sez) (TPyP=5,10,15,20-tetra(4-pyridyl)porphyrin, sez=1,2,5-benzoselenadiazole-5-carboxylate). The coordination polymer may be described as a hexagonal porphyrin nanotube (PNT) and has the potential to bind guest molecules through chalcogen bonding. Single crystal X-ray diffraction (SCXRD) data indicate an internal pore diameter ~9 Å which represents ~35 % of the crystal volume.

The Adipokinetic Hormone (AKH) and the Adipokinetic Hormone/Corazonin-Related Peptide (ACP) Signalling Systems of the Yellow Fever Mosquito : Chemical Models of Binding.

Neuropeptides are the main regulators of physiological, developmental, and behavioural processes in insects. Three insect neuropeptide systems, the adipokinetic hormone (AKH), corazonin (Crz), and adipokinetic hormone/corazonin-related peptide (ACP), and their cognate receptors, are related to the vertebrate gonadotropin (GnRH) system and form the GnRH superfamily of peptides. In the current study, the two signalling systems, AKH and ACP, of the yellow fever mosquito, , were comparatively investigated with respect to ligand binding to their respective receptors.

Precision peptide theranostics: developing - to -terminus optimized theranostics targeting cholecystokinin-2 receptor.

Peptides are ideal for theranostic development as they afford rapid target accumulation, fast clearance from background tissue, and exhibit good tissue penetration. Previously, we developed a novel series of peptides that presented discreet folding propensity leading to an optimal candidate [Ga]Ga-DOTA- ([D-Glu]-Ala-Tyr-MeGly-Trp-MeNle-Asp-Nal-NH) with 50 pM binding affinity against cholecystokinin-2 receptors (CCKR). However, we were confronted with challenges of unfavorably high renal uptake.

NMR techniques for investigating antimicrobial peptides in model membranes and bacterial cells.

AMPs are short, mainly cationic membrane-active peptides found in all living organism. They perform diverse roles including signaling and acting as a line of defense against bacterial infections. AMPs have been extensively investigated as templates to facilitate the development of novel antimicrobial therapeutics.

An Engineered Nanosugar Enables Rapid and Sustained Glucose-Responsive Insulin Delivery in Diabetic Mice.

Glucose-responsive insulin-delivery platforms that are sensitive to dynamic glucose concentration fluctuations and provide both rapid and prolonged insulin release have great potential to control hyperglycemia and avoid hypoglycemia diabetes. Here, biodegradable and charge-switchable phytoglycogen nanoparticles capable of glucose-stimulated insulin release are engineered. The nanoparticles are "nanosugars" bearing glucose-sensitive phenylboronic acid groups and amine moieties that allow effective complexation with insulin (≈95% loading capacity) to form nanocomplexes.

The membrane activity of the antimicrobial peptide caerin 1.1 is pH dependent.

Antimicrobial peptides are an important class of membrane-active peptides that can provide alternatives or complements to classic antibiotics. Among the many classes of AMPs, the histidine-rich family is of particular interest since they may induce pH-sensitive interactions with cell membranes. The AMP caerin 1.

In-cell DNP NMR reveals multiple targeting effect of antimicrobial peptide.

Dynamic nuclear polarization NMR spectroscopy was used to investigate the effect of the antimicrobial peptide (AMP) maculatin 1.1 on cells. The enhanced N NMR signals from nucleic acids, proteins and lipids identified a number of unanticipated physiological responses to peptide stress, revealing that membrane-active AMPs can have a multi-target impact on cells.

Transient RNA Interactions Leave a Covalent Imprint on a Viral Capsid Protein.

The hepatitis B virus (HBV) is the leading cause of persistent liver infections. Its DNA-based genome is synthesized through reverse transcription of an RNA template inside the assembled capsid shell. In addition to the structured assembly domain, the capsid protein harbors a C-terminal extension that mediates both the enclosure of RNA during capsid assembly and the nuclear entry of the capsid during infection.

NMR spectroscopy of lipidic cubic phases.

Lipidic cubic phase (LCP) structures have been used for stabilisation and crystallisation of membrane proteins and show promising properties as drug carriers. In this mini-review, we present how NMR spectroscopy has played a major role in understanding the physico-chemical properties of LCPs and how recent advances in pulsed field gradient NMR techniques open new perspectives in characterising encapsulated molecules.

Enhancing proline-rich antimicrobial peptide action by homodimerization: influence of bifunctional linker.

Antimicrobial peptides (AMPs) are host defense peptides, and unlike conventional antibiotics, they possess potent broad spectrum activities and, induce little or no antimicrobial resistance. They are attractive lead molecules for rational development to improve their therapeutic index. Our current studies examined dimerization of the designed proline-rich AMP (PrAMP), Chex1-Arg20 hydrazide, C-terminal thiol addition to a series of bifunctional benzene or phenyl tethers to determine the effect of orientation of the peptides and linker length on antimicrobial activity.

Multi-Omic Analysis to Characterize Metabolic Adaptation of the Lipidome in Response to Environmental Stress.

As an adaptive survival response to exogenous stress, bacteria undergo dynamic remodelling of their lipid metabolism pathways to alter the composition of their cellular membranes. Here, using as a well characterised model system, we report the development and application of a 'multi-omics' strategy for comprehensive quantitative analysis of the temporal changes in the lipidome and proteome profiles that occur under exponential growth phase versus stationary growth phase conditions i.e.

Systematic comparison of activity and mechanism of antimicrobial peptides against nosocomial pathogens.

The World Health Organisation has deemed several multi-drug resistant (MDR) nosocomial bacterial pathogens to be of significant threat to human health. A stark increase in morbidity, mortality and the burden to healthcare systems around the world can be attributed to the development of resistance in these bacteria. Accordingly, alternative antimicrobial agents have been sought as an attractive means to combat MDR pathogens, with one such example being antimicrobial peptides (AMPs).

Spectroscopic study of L-DOPA and dopamine binding on novel gold nanoparticles towards more efficient drug-delivery system for Parkinson's disease.

Nano-drug delivery systems may potentially overcome current challenges in the treatment of Parkinson's disease (PD) by enabling targeted delivery and more efficient blood-brain penetration ability. This study investigates novel gold nanoparticles (AuNPs) to be used as delivery systems for L-DOPA and dopamine by considering their binding capabilities in the presence and absence of a model protein, bovine serum albumin (BSA). Four different AuNPs were prepared by surface functionalization with polyethylene glycol (PEG), 1-adamantylamine (Ad), 1-adamantylglycine (AdGly), and peptidoglycan monomer (PGM).

The impact of antibacterial peptides on bacterial lipid membranes depends on stage of growth.

The impact of maculatin 1.1 (Mac1) on the mechanical properties of supported lipid membranes derived from exponential growth phase (EGP) and stationary growth phase (SGP) lipid extracts was analysed by surface plasmon resonance and atomic force microscopy. Each membrane was analysed by quantitative nanomechanical mapping to derive measurements of the modulus, adhesion and deformation in addition to bilayer height.

TOAC spin-labeled peptides tailored for DNP-NMR studies in lipid membrane environments.

The benefit of combining in-cell solid-state dynamic nuclear polarization (DNP) NMR and cryogenic temperatures is providing sufficient signal/noise and preservation of bacterial integrity via cryoprotection to enable in situ biophysical studies of antimicrobial peptides. The radical source required for DNP was delivered into cells by adding a nitroxide-tagged peptide based on the antimicrobial peptide maculatin 1.1 (Mac1).

Utilizing magnetic resonance techniques to study membrane interactions of amyloid peptides.

Alzheimer's disease (AD) is a common neurodegenerative condition that involves the extracellular accumulation of amyloid plaques predominantly consisting of Aβ peptide aggregates. The amyloid plaques and soluble oligomeric species of Aβ are believed to be the major cause of synaptic dysfunction in AD brain and their cytotoxic mechanisms have been proposed to involve interactions with cell membranes. In this review, we discuss our solid-state nuclear magnetic resonance (ssNMR) studies of Aβ interactions with model membranes.

C-terminus amidation influences biological activity and membrane interaction of maculatin 1.1.

Cationic antimicrobial peptides have been investigated for their potential use in combating infections by targeting the cell membrane of microbes. Their unique chemical structure has been investigated to understand their mode of action and optimize their dose-response by rationale design. One common feature among cationic AMPs is an amidated C-terminus that provides greater stability against in vivo degradation.

Expression and purification of the native C-amidated antimicrobial peptide maculatin 1.1.

Maculatin 1.1 (Mac1) is an antimicrobial peptide (AMP) from an Australian tree frog and exhibits low micromolar activity against Gram-positive bacteria. The antimicrobial properties of Mac1 are linked to its disruption of bacterial lipid membranes, which has been studied extensively by in vitro nuclear magnetic resonance (NMR) spectroscopy and biophysical approaches.

A New Turn in Peptide-Based Imaging Agents: Foldamers Afford Improved Theranostics Targeting Cholecystokinin-2 Receptor-Positive Cancer.

Proteins adopt unique folded secondary and tertiary structures that are responsible for their remarkable biological properties. This structural complexity is key in designing efficacious peptides that can mimic the three-dimensional structure needed for biological function. In this study, we employ different chemical strategies to induce and stabilize a β-hairpin fold of peptides targeting cholecystokinin-2 receptors for theranostic application (combination of a targeted therapeutic and a diagnostic companion).

Structural Disruptions of the Outer Membranes of Gram-Negative Bacteria by Rationally Designed Amphiphilic Antimicrobial Peptides.

Gram-negative bacteria are covered by both an inner cytoplasmic membrane (IM) and an outer membrane (OM). Antimicrobial peptides (AMPs) must first permeate through the OM and cell wall before attacking the IM to cause cytoplasmic leakage and kill the bacteria. The bacterial OM is an asymmetric bilayer with the outer leaflet primarily composed of lipopolysaccharides (LPSs) and the inner leaflet composed of phospholipids (PLs).

In-cell Solid-State NMR Studies of Antimicrobial Peptides.

Antimicrobial peptides (AMPs) have attracted attention as alternatives to classic antibiotics due to their expected limited pressure on bacterial resistance mechanisms. Yet, their modes of action, in particular , remain to be elucidated. atomistic-scale details of complex biomolecular assemblies is a challenging requirement for deciphering the complex modes of action of AMPs.

How do Self-Assembling Antimicrobial Lipopeptides Kill Bacteria?

Antimicrobial peptides are promising alternatives to traditional antibiotics. A group of self-assembling lipopeptides was formed by attaching an acyl chain to the N-terminus of α-helix-forming peptides with the sequence C-G(IIKK)I-NH (CG, = 4-12 and = 2). CG self-assemble into nanofibers above their critical aggregation concentrations (CACs).

The Location of the Antimicrobial Peptide Maculatin 1.1 in Model Bacterial Membranes.

Maculatin 1.1 (Mac1) is an antimicrobial peptide (AMP) from the skin secretions of Australian tree frogs. In this work, the interaction of Mac1 with anionic phospholipid bilayers was investigated by NMR, circular dichroism (CD) spectroscopy, neutron reflectometry (NR) and molecular dynamics (MD).

A multifunctional surfactant catalyst inspired by hydrolases.

The remarkable power of enzymes to undertake catalysis frequently stems from their grouping of multiple, complementary chemical units within close proximity around the enzyme active site. Motivated by this, we report here a bioinspired surfactant catalyst that incorporates a variety of chemical functionalities common to hydrolytic enzymes. The textbook hydrolase active site, the catalytic triad, is modeled by positioning the three groups of the triad (-OH, -imidazole, and -COH) on a single, trifunctional surfactant molecule.

The antimicrobial peptide maculatin self assembles in parallel to form a pore in phospholipid bilayers.

Little is known experimentally about the detailed orientation of membrane-bound maculatin 1.1 (Mac1), an antimicrobial peptide from the skin secretions of Australian tree frogs. In this work multiple N-labelled or H-labelled Mac1 with dodecylphosphocholine (DPC) micelles and isotropic DMPC/DHPC (q = 0.