In vitro treatment with liposome-encapsulated Mannose-1-phosphate restores N-glycosylation in PMM2-CDG patient-derived fibroblasts.

PMM2-CDG is the most common congenital disorder of glycosylation (CDG). Patients with this disease often carry compound heterozygous mutations of the gene encoding the phosphomannomutase 2 (PMM2) enzyme. PMM2 converts mannose-6-phosphate (M6P) to mannose-1-phosphate (M1P), which is a critical upstream metabolite for proper protein N-glycosylation. Therapeutic options for PMM2-CDG patients are limited to management of the disease symptoms, as no drug is currently approved to treat this disease. GLM101 is a M1P-loaded liposomal formulation being developed as a candidate drug to treat PMM2-CDG. This report describes the effect of GLM101 treatment on protein N-glycosylation of PMM2-CDG patient-derived fibroblasts. This treatment normalized intracellular GDP-mannose, increased the relative glycoprotein mannosylation content and TNFα-induced ICAM-1 expression. Moreover, glycomics profiling revealed that GLM101 treatment of PMM2-CDG fibroblasts resulted in normalization of most high mannose glycans and partial correction of multiple complex and hybrid glycans. In vivo characterization of GLM101 revealed its favorable pharmacokinetics, liver-targeted biodistribution, and tolerability profile with achieved systemic concentrations significantly greater than its effective in vitro potency. Taken as a whole, the results described in this report support further exploration of GLM101's safety, tolerability, and efficacy in PMM2-CDG patients.

Band Gap Engineering in a 2D Material for Solar-to-Chemical Energy Conversion.

The electronic structure of 2D semiconductors depends on their thickness, providing new opportunities to engineer semiconductors for energy conversion, electronics, and catalysis. Here we show how a 3D semiconductor, black phosphorus, becomes active for solar-to-chemical energy conversion when it is thinned to a 2D material. The increase in its band gap, from 0.3 eV (3D) to 2.1 eV (2D monolayer), is accompanied by a 40-fold enhancement in the formation of chemical products. Despite this enhancement, smaller flakes also have shorter excited state lifetimes. We deduce a mechanism in which recombination occurs at flake edges, while the "van der Waals" surface of black phosphorus bonds to chemical intermediates and facilitates electron transfer. The unique properties of black phosphorus highlight its potential as a customizable material for solar energy conversion and catalysis, while also allowing us to identify design rules for 2D photocatalysts that will enable further improvements in these materials.