Glycosaminoglycans: What Remains To Be Deciphered?

Glycosaminoglycans (GAGs) are complex polysaccharides exhibiting a vast structural diversity and fulfilling various functions mediated by thousands of interactions in the extracellular matrix, at the cell surface, and within the cells where they have been detected in the nucleus. It is known that the chemical groups attached to GAGs and GAG conformations comprise “glycocodes” that are not yet fully deciphered. The molecular context also matters for GAG structures and functions, and the influence of the structure and functions of the proteoglycan core proteins on sulfated GAGs and vice versa warrants further investigation. The lack of dedicated bioinformatic tools for mining GAG data sets contributes to a partial characterization of the structural and functional landscape and interactions of GAGs. These pending issues will benefit from the development of new approaches reviewed here, namely (i) the synthesis of GAG oligosaccharides to build large and diverse GAG libraries, (ii) GAG analysis and sequencing by mass spectrometry (e.g., ion mobility-mass spectrometry), gas-phase infrared spectroscopy, recognition tunnelling nanopores, and molecular modeling to identify bioactive GAG sequences, biophysical methods to investigate binding interfaces, and to expand our knowledge and understanding of glycocodes governing GAG molecular recognition, and (iii) artificial intelligence for in-depth investigation of GAGomic data sets and their integration with proteomics

Efficacy of CG 3 R 6 TAT Nanoparticles Self-Assembled from a Novel Antimicrobial Peptide for theTreatment of Candida albicans Meningitis in Rabbits

Background: Candidal meningitis is a common clinical manifestation of invasive candidiasis in neonates. The aim of this study was to evaluate the in vivo antifungal efficacy of CG3R6TAT nanoparticles, novel core-shell structures self-assembled from cationic antimicrobial peptides, in a rabbit model of candidal meningitis. Methods: In vitro activity of CG3R6TAT nanoparticles against Candida albicans was assessed by determining the minimum inhibitory concentration and kill-time curves. In vivo, intravenous treatment with CG3R6TAT nanoparticles (n = 6; 0.25 mg/kg/day) or fluconazole (n = 6; 100 mg/kg/day) began 3 days after infection and continued for 11 consecutive days; the efficacy was assessed following 11 days of treatment by yeast counting in cerebrospinal fluid (CSF), the leukocyte concentrations in CSF and the histopathology of brain parenchyma. Results: At a concentration three times higher than the minimum inhibitory concentration (8.1 µmol/l), the nanoparticles completely sterilized C. albicans after 5 h of incubation. In addition, there was a significant reduction in fungal counts and leukocyte concentrations in the CSF from rabbits treated with CG3R6TAT nanoparticles or fluconazole versus those from untreated control rabbits (p 0.05, vs. control). The histopathologic severity of rabbits was significantly attenuated after CG3R6TAT treatment (p = 0.001, vs. control). Conclusion: This study suggests that CG3R6TAT nanoparticles may be a promising therapeutic agent for candidal meningitis