Identification of Potential Drug Targets of Calix[4]arene by Reverse Docking.

Calixarenes are displaying great potential for the development of new drug delivery systems, diagnostic imaging, biosensing devices and inhibitors of biological processes. In particular, calixarene derivatives are able to interact with many different enzymes and function as inhibitors. By screening of the potential drug target database (PDTD) with a reverse docking procedure, we identify and discuss a selection of 100 proteins that interact strongly with calix[4]arene.

Interaction of Au(III) with amino acids: a vade mecum for medicinal chemistry and nanotechnology.

Au(III) is highly reactive. At odds with its reduced counterpart, Au(I), it is hardly present in structural databases. And yet, it is the starting reactant to form gold nanoclusters (AuNCs) and the constitutive component of a new class of drugs.

Selective ion transport in large-area graphene oxide membrane filters driven by the ionic radius and electrostatic interactions.

Filters made of graphene oxide (GO) are promising for purification of water and selective sieving of specific ions; while some results indicate the ionic radius as the discriminating factor in the sieving efficiency, the exact mechanism of sieving is still under debate. Furthermore, most of the reported GO filters are planar coatings with a simple geometry and an area much smaller than commercial water filters. Here, we show selective transport of different ions across GO coatings deposited on standard hollow fiber filters with an area >10 times larger than typical filters reported.

In Vivo Application of Carboranes for Boron Neutron Capture Therapy (BNCT): Structure, Formulation and Analytical Methods for Detection.

Carboranes have emerged as one of the most promising boron agents in boron neutron capture therapy (BNCT). In this context, in vivo studies are particularly relevant, since they provide qualitative and quantitative information about the biodistribution of these molecules, which is of the utmost importance to determine the efficacy of BNCT, defining their localization and (bio)accumulation, as well as their pharmacokinetics and pharmacodynamics. First, we gathered a detailed list of the carboranes used for in vivo studies, considering the synthesis of carborane derivatives or the use of delivery system such as liposomes, micelles and nanoparticles.

Rational design and synthesis of lumican stapled peptides for promoting corneal wound healing.

Purpose: Lumican is a major extracellular matrix (ECM) component in the cornea that is upregulated after injury and promotes corneal wound healing. We have recently shown that peptides designed based on the 13 C-terminal amino acids of lumican (LumC13 and LumC13) are able to recapitulate the effects of lumican on promoting corneal wound healing. Herein we used computational chemistry to develop peptide mimetics derived from LumC13 with increased stability and half-life that are biologically active and non-toxic, thereby promoting corneal wound healing with increased pharmacological potential.

Robust Biosensor Based on Carbon Nanotubes/Protein Hybrid Electrolyte Gated Transistors.

Semiconducting single walled carbon nanotubes (SWCNTs) are promising materials for biosensing applications with electrolyte-gated transistors (EGT). However, to be employed in EGT devices, SWCNTs often require lengthy solution-processing fabrication techniques. Here, we introduce a simple solution-based method that allows fabricating EGT devices from stable dispersions of SWCNTs/bovine serum albumin (BSA) hybrids in water.

Exploiting Blood Transport Proteins as Carborane Supramolecular Vehicles for Boron Neutron Capture Therapy.

Carboranes are promising agents for applications in boron neutron capture therapy (BNCT), but their hydrophobicity prevents their use in physiological environments. Here, by using reverse docking and molecular dynamics (MD) simulations, we identified blood transport proteins as candidate carriers of carboranes. Hemoglobin showed a higher binding affinity for carboranes than transthyretin and human serum albumin (HSA), which are well-known carborane-binding proteins.

Identification and Biological Evaluation of a Water-Soluble Fullerene Nanomaterial as BTK Kinase Inhibitor.

Introduction: Thanks to recent advances in synthetic methodology, water-soluble fullerene nanomaterials that interfere with biomolecules, especially DNA/RNA and selected proteins, have been found with tremendous potential for applications in nanomedicine. Herein, we describe the synthesis and evaluation of a water-soluble glycine-derived [60]fullerene hexakisadduct (HDGF) with T symmetry, which is a first-in-class BTK protein inhibitor.

Methods: We synthesized and characterized glycine derived [60]fullerene using NMR, ESI-MS, and ATR-FT-IR.

Identification of Blood Transport Proteins to Carry Temoporfin: A Domino Approach from Virtual Screening to Synthesis and In Vitro PDT Testing.

Temoporfin (mTHPC) is one of the most promising photosensitizers used in photodynamic therapy (PDT). Despite its clinical use, the lipophilic character of mTHPC still hampers the full exploitation of its potential. Low solubility in water, high tendency to aggregate, and low biocompatibility are the main limitations because they cause poor stability in physiological environments, dark toxicity, and ultimately reduce the generation of reactive oxygen species (ROS).

Dissecting the Interactions between Chlorin e6 and Human Serum Albumin.

Chlorin e6 (Ce6) is among the most used sensitizers in photodynamic (PDT) and sonodynamic (SDT) therapy; its low solubility in water, however, hampers its clinical exploitation. Ce6 has a strong tendency to aggregate in physiological environments, reducing its performance as a photo/sono-sensitizer, as well as yielding poor pharmacokinetic and pharmacodynamic properties. The interaction of Ce6 with human serum albumin (HSA) (i) governs its biodistribution and (ii) can be used to improve its water solubility by encapsulation.

Light-Enhanced Cytotoxicity of Doxorubicin by Photoactivation.

The combination of photodynamic therapy with chemotherapy (photochemotherapy, PCT) can lead to additive or synergistic antitumor effects. Usually, two different molecules, a photosensitizer (PS) and a chemotherapeutic drug are used in PCT. Doxorubicin is one of the most successful chemotherapy drugs.

Carrying Temoporfin with Human Serum Albumin: A New Perspective for Photodynamic Application in Head and Neck Cancer.

Temoporfin (mTHPC) is approved in Europe for the photodynamic treatment of head and neck squamous cell carcinoma (HNSCC). Although it has a promising profile, its lipophilic character hampers the full exploitation of its potential due to high tendency of aggregation and a reduced ROS generation that compromise photodynamic therapy (PDT) efficacy. Moreover, for its clinical administration, mTHPC requires the presence of ethanol and propylene glycol as solvents, often causing adverse effects in the site of injection.

Deciphering the Reactive Pathways of Competitive Reactions inside Carbon Nanotubes.

Nanoscale control of chemical reactivity, manipulation of reaction pathways, and ultimately driving the outcome of chemical reactions are quickly becoming reality. A variety of tools are concurring to establish such capability. The confinement of guest molecules inside nanoreactors, such as the hollow nanostructures of carbon nanotubes (CNTs), is a straightforward and highly fascinating approach.

Enhanced Uptake and Phototoxicity of C@albumin Hybrids by Folate Bioconjugation.

Fullerenes are considered excellent photosensitizers, being highly suitable for photodynamic therapy (PDT). A lack of water solubility and low biocompatibility are, in many instances, still hampering the full exploitation of their potential in nanomedicine. Here, we used human serum albumin (HSA) to disperse fullerenes by binding up to five fullerene cages inside the hydrophobic cavities.

Facile high-yield synthesis and purification of lysine-modified graphene oxide for enhanced drinking water purification.

Lysine-covalently modified graphene oxide (GO-Lys) was prepared by an innovative procedure. Lysine brushes promote enhanced adsorption of bisphenol A, benzophenone-4 and carbamazepine contaminants from tap water, with a removal capacity beyond the state of the art.

Fullerenes against COVID-19: Repurposing C and C to Clog the Active Site of SARS-CoV-2 Protease.

The persistency of COVID-19 in the world and the continuous rise of its variants demand new treatments to complement vaccines. Computational chemistry can assist in the identification of moieties able to lead to new drugs to fight the disease. Fullerenes and carbon nanomaterials can interact with proteins and are considered promising antiviral agents.

Dissecting the Supramolecular Dispersion of Fullerenes by Proteins/Peptides: Amino Acid Ranking and Driving Forces for Binding to C.

Molecular dynamics simulations were used to quantitatively investigate the interactions between the twenty proteinogenic amino acids and C. The conserved amino acid backbone gave a constant energetic interaction ~5.4 kcal mol, while the contribution to the binding due to the amino acid side chains was found to be up to ~5 kcal mol for tryptophan but lower, to a point where it was slightly destabilizing, for glutamic acid.

Structural Determinants of Substrate Recognition and Catalysis by Heparan Sulfate Sulfotransferases.

Heparan sulfate (HS) and heparin contain imprinted "sulfation codes", which dictate their diverse physiological and pathological functions. A group of orchestrated biosynthetic enzymes cooperate in polymerizing and modifying HS chains. The biotechnological development of enzymes that can recreate this sulfation pattern on synthetic heparin is challenging, primarily due to the paucity of quantitative data for sulfotransferase enzymes.

Core-shell graphene oxide-polymer hollow fibers as water filters with enhanced performance and selectivity.

Commercial hollow fiber filters for micro- and ultrafiltration are based on size exclusion and do not allow the removal of small molecules such as antibiotics. Here, we demonstrate that a graphene oxide (GO) layer can be firmly immobilized either inside or outside polyethersulfone-polyvinylpyrrolidone hollow fiber (Versatile PES®, hereafter PES) modules and that the resulting core-shell fibers inherits the microfiltration ability of the pristine PES fibers and the adsorption selectivity of GO. GO nanosheets were deposited on the fiber surface by filtration of a GO suspension through a PES cartridge (cut-off 0.

Inhibition of α-chymotrypsin by pristine single-wall carbon nanotubes: Clogging up the active site.

The preferred spatial orientation of single-wall carbon nanotubes (SWCNTs) in their interaction with enzymes determines their behavior either as nano-supports or as inhibitors. α -chymotrypsin (α-CT) is considered a serine protease model for studying nanomaterial/proteases interactions. The interaction of α-CT with pristine single-wall carbon nanotubes is still unknown.

Stable and Biocompatible Monodispersion of C in Water by Peptides.

The lack of solubility in water and the formation of aggregates hamper many opportunities for technological exploitation of C. Here, different peptides were designed and synthesized with the aim of monomolecular dispersion of C in water. Phenylalanines were used as recognizing moieties, able to interact with C through π-π stacking, while a varying number of glycines were used as spacers, to connect the two terminal phenylalanines.

A Full QM Computational Study of the Catalytic Mechanism of α-1,4-Glucan Lyases.

We investigated the catalytic mechanism of α-1,4-glucan lyases using a full QM DFT approach based on the M06-2X functional. The reaction profile of the whole catalytic process can be divided into three phases: glycosylation, deglycosylation-elimination and tautomerization. Glycosylation is a highly asynchronous S 1-like process with an energy barrier of 10.

The Reaction Pathway of Cellulose Pyrolysis to a Multifunctional Chiral Building Block: The Role of Water Unveiled by a DFT Computational Investigation.

LAC (hydroxylactone (1R,5S)-1-hydroxy-3,6-dioxabicyclo[3.2.1]octan-2-one) is one of the most interesting products of the pyrolysis of cellulose and represents a useful chiral building block in organic synthesis.

Computational Evidence for the Catalytic Mechanism of Tyrosylprotein Sulfotransferases: A Density Functional Theory Investigation.

In this paper we have examined the mechanism of tyrosine O-sulfonation catalyzed by human TPST-2. Our computations, in agreement with Teramoto's hypothesis, indicate a concerted SN2-like reaction (with an activation barrier of 18.2 kcal mol(-1)) where the tyrosine oxygen is deprotonated by Glu(99) (base catalyst) and simultaneously attacks as a nucleophile the sulfuryl group.