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We describe the chemical synthesis of the fungal naphthopyrones YWA1 and fonsecin B, as well as their functionalization with an amine-spacer arm and the conjugation of the resulting molecules to three different functional tags (i.e., biotin, Oregon green, 1-[3-(succinimidyloxycarbonyl)benzyl]-4-[5-(4-methoxyphenyl)-2-oxazolyl]pyridinium bromide (PyMPO)). The naphthopyrone-biotin and -PyMPO constructs maintained the ability to bind the C-type lectin receptor MelLec, whose interaction with immunologically active fungal metabolites (i.e., 1,8-dihydroxynaphthalene-(DHN)-melanin and YWA1) is a key step in host recognition and induction of protective immune responses against Aspergillus fumigatus. The fluorescent Fonsecin B-PyMPO construct 21was used to selectively visualize MelLec-expressing cells, thus validating the potential of this strategy for studying the role and functions of MelLec in immunity.

A significant percentage of costs in pharmaceutical markets is devoted to supplements due to the confidence of consumers in the beneficial effects of these products. Magnesium is one of the supplements with enduring and increasing popularity. According to what is reported online, this metal ion can cure or prevent almost all kinds of diseases. This review aims at illustrating a series of scientifically demonstrated cases in which magnesium was used in clinical practice. Except for its ordinary use as antacid and laxative, other ascertained uses, reported in scientific literature, consist of helping to treat several diseases such as nocturnal leg cramps, pre-eclampsia, diabetes, depression, Parkinsons and Alzheimers disease, hypertension, some types of arrhythmias, asthma, migraine headaches, epilepsy, cerebral haemorrhage, and stroke. However, many of these promising uses of magnesium require further studies to define the involved molecular mechanisms which should help establishing its uses in relation to the prolonged use of supplements.

The tetrazine/trans-cyclooctene (TCO) inverse electron-demand Diels–Alder (IEDDA) reaction is the fastest bioorthogonal “click” ligation process reported to date. In this context, TCO reagents have found widespread applications; however, their availability and structural diversity is still somewhat limited due to challenges connected with their synthesis and structural modification. To address this issue, we developed a novel strategy for the conjugation of TCO derivatives to a biomolecule, which allows for the creation of greater structural diversity from a single precursor molecule, i.e., trans,trans-1,5-cyclooctadiene [(E,E)-COD] 1, whose preparation requires standard laboratory equipment and readily available reagents. This two-step strategy relies on the use of new bifunctional TCO linkers (5a–11a) for IEDDA reactions, which can be synthesized via 1,3-dipolar cycloaddition of (E,E)-COD 1with different azido spacers (5–11) carrying an electrophilic function (NHS-ester, N-succinimidyl carbonate, p-nitrophenyl-carbonate, maleimide) in the ω-position. Following bioconjugation of these electrophilic linkers to the nucleophilic residue (cysteine or lysine) of a protein (step 1), the resulting TCO-decorated constructs can be subjected to a IEDDA reaction with tetrazines functionalized with fluorescent or near-infrared (NIR) tags (step 2). We successfully used this strategy to label bovine serum albumin with the TCO linker 8aand subsequently reacted it in a cell lysate with the fluorescein-isothiocyanate (FITC)-derived tetrazine 12. The same strategy was then used to label the bacterial wall of Gram-positive Staphylococcus aureus, showing the potential of these linkers for live-cell imaging. Finally, we determined the impact of structural differences of the linkers upon the stability of the bioorthogonal constructs. The compounds for stability studies were prepared by conjugation of TCO linkers 6a, 8a, and 10ato mAbs, such as Rituximab and Obinutuzumab, and subsequent labeling with a reactive Cy3-functionalized tetrazine.

Resistance to infection is critically dependent on the ability of pattern recognition receptors to recognize microbial invasion and induce protective immune responses. One such family of receptors are the C-type lectins, which are central to antifungal immunity. These receptors activate key effector mechanisms upon recognition of conserved fungal cell-wall carbohydrates. However, several other immunologically active fungal ligands have been described; these include melanin, for which the mechanism of recognition is hitherto undefined. Here we identify a C-type lectin receptor, melanin-sensing C-type lectin receptor (MelLec), that has an essential role in antifungal immunity through recognition of the naphthalene-diol unit of 1,8-dihydroxynaphthalene (DHN)-melanin. MelLec recognizes melanin in conidial spores of Aspergillus fumigatus as well as in other DHN-melanized fungi. MelLec is ubiquitously expressed by CD31+endothelial cells in mice, and is also expressed by a sub-population of these cells that co-express epithelial cell adhesion molecule and are detected only in the lung and the liver. In mouse models, MelLec was required for protection against disseminated infection with A. fumigatus. In humans, MelLec is also expressed by myeloid cells, and we identified a single nucleotide polymorphism of this receptor that negatively affected myeloid inflammatory responses and significantly increased the susceptibility of stem-cell transplant recipients to disseminated Aspergillus infections. MelLec therefore recognizes an immunologically active component commonly found on fungi and has an essential role in protective antifungal immunity in both mice and humans.

The de novo design of peptides and proteins represents an innovative tool in the early stage of drug research. Over the last thirty years, many studies have been undertaken to develop new strategies of design and synthesis of peptides with specific conformations. Substituted amino acids exhibit significant biological activity, and play an important role in medicinal chemistry. Proline chimeras in particular, are valuable tools for biological investigations. In the literature several strategies for the synthesis of this chimeras are reported. Here we will focus on Tryptophan-Proline and summarize useful methodologies that can be applied to their preparation.

Ordered mesoporous materials (OMMs) are interesting matrixes for nanomedicine applications such as innovative drug delivery systems. Here, we compare the behavior of the widely studied SBA-15 mesoporous silica with that of the less investigated MSE (a periodic mesoporous organosilica whose silicon atoms are alternatively connected by means of −Si−O−Si− and −Si−CH2−CH2−Si− groups) toward the adsorption (pH 7.0 and 9.6) and in vitro release (pH 7.4; T= 37 °C) of an antimicrobial protein (hen egg white lysozyme). Both OMMs have a hexagonal ordered mesoporous structure and texture, as confirmed by SAXS, TEM, and N2adsorption isotherms, but differ for the chemical composition and surface charge density, as determined by ATR-FTIR spectroscopy and potentiometric titrations, respectively. Rather than the structural and textural features, the different chemical composition of SBA-15 and MSE seems to be responsible for the different lysozyme loading and release and for the different stability toward the lixiviating action of the physiological medium (pH 7.4; T= 37 °C).