Bethesda Declaration urges reversal of recent policies, including funding cuts

Sialic acids (Sias), consisting primarily of N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), play crucial roles in many biological processes. The detection and quantification of Sias are essential for understanding their roles in health and disease progression. Although numerous techniques have been developed to enhance the specificity and sensitivity of Sias analysis, traditional methods such as derivatization with fluorescent tags coupled with HPLC-MS analysis often suffer from low limits of detection, limiting the quantification of Sias in trace samples. Here, we introduce DAPMI, a novel imidazolium-based ITag for sensitive Sia detection. We demonstrate its utility in the detection and quantification of Sia composition in human serum, and in different tissues from CMAH (cytidine monophosphate-N-acetylneuraminic acid hydroxylase) knockout mice, using ESI-MS analysis and with a limit of detection (LOD) down to the low fmol range. The results showed that both Neu5Ac and Neu5Gc were present in varying proportions in wild-type mice and CMAH heterogeneous mice. Trace amounts of Neu5Gc were also detected in the tissues of CMAH null homogeneous mice (CMAH–/−) and in human blood serum using ESI-ToF-MS, suggesting its presence may be linked to dietary intake of Neu5Gc-containing foods, as Neu5Gc cannot be synthesized endogenously in CMAH–/– mice, and in humans. The DAPMI-ITag and the labeling technology developed in this study significantly improve the sensitivity of Sias detection compared to conventional tags such as o-phenylenediamine (OPD), and provide a new chemical tool for the exploration of Sias’ biological roles and their use as biomarkers in different human conditions.

Glycobiology is rooted in the study of monosaccharides, Angstrom-sized molecules that are the building blocks of intricate glycosylation patterns. Glycosylated biomolecules form the glycocalyx, a dens...

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Qiu et al. identify that reduced mannose metabolism is a key characteristic of T cell dysfunction. Enhancing mannose metabolism in T cells through D-mannose supplementation boosts anti-tumor activity, limits exhaustion differentiation, and maintains T cell stemness. Mechanistically, D-mannose promotes the OGT-mediated O-GlcNAcylation and stabilization of β-catenin, enhancing T cell stemness.

Molecular conjugation to antibodies has emerged as a growing strategy to combine the mechanistic activities of the attached molecule with the specificity of antibodies. A variety of technologies have been applied for molecular conjugation; however, these approaches face several limitations, including disruption of antibody structure, destabilization of the antibody, and/or heterogeneous conjugation patterns. Collectively, these challenges lead to reduced yield, purity, and function of conjugated antibodies.

Ebola and Marburg (EBOV and MARV) filoviral infections lead to fatal hemorrhagic fevers and have caused over 30 outbreaks in the last 50 years. Currently, there are no FDA-approved small molecule therapeutics for effectively treating filoviral diseases. To address this unmet medical need, we have conducted a systematic structural optimization of an early lead compound, N-(4-(4-methylpiperidin-1-yl)-3-(trifluoromethyl)phenyl)-4-(morpholinomethyl)benzamide (1), borne from our previously reported hit-to-lead effort. This secondary round of structure–activity relationship (SAR) involved the design and synthesis of several deconstructed and reconstructed analogs of compound 1, which were then tested against pseudotyped EBOV and MARV. The antiviral activities of the most promising leads were further validated in infectious assays. The optimized analogs exhibited desirable antiviral activity against different ebolaviruses and reduced off-target activity. Additionally, they also possessed druglike properties, that make them ideal candidates for in vivo efficacy studies as part of our ongoing drug discovery campaign against EBOV and MARV.

This study explores how viral N-linked glycans play a role in the interaction between chloroviruses glycoproteins and key receptors of the innate immune system.

Palleon Pharmaceuticals, a company pioneering glyco-immunology drug development to treat autoimmune diseases and cancer, today announced a collaborati