Sulfoglycolipids and Related Analogues of Mycobacterium tuberculosis: Chemical Synthesis and Immunological Studies.

Mycobacterium tuberculosis (Mtb) causes tuberculosis as one major threat to human health, which has been deteriorated owing to the emerging multidrug resistance. Mtb contains a complex lipophilic cell wall structure that is important for bacterial persistence. Among the lipid components, sulfoglycolipids (SGLs), known to induce immune cell responses, are composed of a trehalose core attached with a conserved sulfate group and 1-4 fatty acyl chains in an asymmetric pattern. At least one of these acyl chains is polymethylated with 3-12 methyl branches. Although Mtb SGL can be isolated from bacterial culture, resulting SGL is still a homologous mixture, impeding accurate research studies. This up-to-date review covers the chemical synthesis and immunological studies of Mtb SGLs and structural analogues, with an emphasis on the development of new glycosylation methods and the asymmetric synthesis of polymethylated scaffolds. Both are critical to advance further research on biological functions of these complicated SGLs.

Bioevaluation of sixteen ADMDP stereoisomers toward alpha-galactosidase A: Development of a new pharmacological chaperone for the treatment of Fabry disease and potential enhancement of enzyme replacement therapy efficiency.

A unique molecular library consisting of all sixteen synthetic ADMDP (1-aminodeoxy-DMDP) stereoisomers has been prepared and evaluated for inhibitory activity against α-Gal A, and ability to impart thermal stabilization of this enzyme. The results of this testing led us to develop a novel pharmacological chaperone for the treatment of Fabry disease. 3-Epimer ADMDP was found to be an effective pharmacological chaperone, able to rescue α-Gal A activity in the lymphoblast of the N215S Fabry patient-derived cell line, without impairment of cellular ß-galactosidase activity. When 3-epimer ADMDP was administered with rh-α-Gal A (enzyme replacement therapy) for the treatment of Fabry patient-derived cell lines, improvements in the efficacy of rh-α-Gal A was observed, which suggests this small molecule can also provide clinical benefit of enzyme replacement therapy in Fabry disease.

Substitutionally doped phosphorene: electronic properties and gas sensing.

Phosphorene, a new elemental two-dimensional material, has attracted increasing attention owing to its intriguing electronic properties. In particular, pristine phospohorene, due to its ultrahigh surface-volume ratio and high chemical activity, has been shown to be promising for gas sensing (Abbas et al 2015 ACS Nano 9 5618). To further enhance its sensing ability, we perform first-principles calculations based on density functional theory to study substitutionally doped phosphorene with 17 different atoms, focusing on structures, energetics, electronic properties and gas sensing. Our calculations reveal that anionic X (X = O, C and S) dopants have a large binding energy and highly dispersive electronic states, signifying the formation of covalent X-P bonds and thus strong structural stability. Alkali atom (Li and Na) doping is found to donate most of the electrons in the outer s-orbital by forming ionic bonds with P, and the band gap decreases by pushing down the conduction band, suggesting that the optical and electronic properties of the doped phosphorene can be tailored. For doping with VIIIB-group (Fe, Co and Ni) elements, a strong affinity is predicted and the binding energy and charge transfer are correlated strongly with their electronegativity. By examining NO molecule adsorption, we find that these metal doped phosphorenes (MDPs) in general exhibit a significantly enhanced chemical activity compared with pristine phosphorene. Our study suggests that substitutionally doped phosphorene shows many intriguing electronic and optic properties different from pristine phosphorene and MDPs are promising in chemical applications involving molecular adsorption and desorption processes, such as materials growth, catalysis, gas sensing and storage.

Synthesis of Diverse N-Substituted Muramyl Dipeptide Derivatives and Their Use in a Study of Human NOD2 Stimulation Activity.

A flexible synthetic strategy toward the preparation of diverse N-substituted muramyl dipeptides (N-substituted MDPs) from different protected monosaccharides is described. The synthetic MDPs include N-acetyl MDP and N-glycolyl MDP, known NOD2 ligands, and this methodology allows for structural variation at six positions, including the muramic acid, peptide, and N-substituted moieties. The capacity of these molecules to activate human NOD2 in the innate immune response was also investigated. It was found that addition of the methyl group at the C1 position of N-glycolyl MDP significantly enhanced the NOD2 stimulating activity.