https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/22 Principal Investigator- Dr. Srinivasa Gopalan Sampathkumar 2026-04-03T16:52:19Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1502 Title: An expeditious synthesis of novel DNA nucleobase mimics of (+)-anisomycin Authors: Sampathkumar, Srinivasa-Gopalan; Sanghvi, Yogesh S; Abhiraj, R; Mishra, Umesh K; Ramesh, Namakkal G Abstract: A glycal based expeditious synthesis of novel nucleoside analogues of (+)-anisomycin is reported. Readily available tri-O-benzyl-D-glucal was converted to a partially protected trihydroxypyrrolidine that is used as a common scaffold for the introduction of various nucleobases at the primary hydroxyl centre. Nucleoside analogues possessing all four DNA bases have been synthesized. Selective acetylation at C3 position was carried out with two of these unnatural nucleosides in order to mimic the structure of (+)-anisomycin. Cytotoxicity studies of some of these nucleosides showed that they display weaker activity on HeLa cells than Ara-C. 2022-01-01T00:00:00Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1275 Title: Efficient inhibition of O-glycan biosynthesis using the hexosamine analog Ac5GalNTGc Authors: Sampathkumar, Srinivasa-Gopalan; Neelamegham, Sriram; Wang, Shuen-Shiuan; Solar, Virginia Del; Yu, Xinheng; Antonopoulos, Aristotelis; Friedman, Alan E; Agarwal, Kavita; Garg, Monika; Ahmed, Syed Meheboob; Addhya, Ahana; Nasirikenari, Mehrab; Lau, Joseph T; Dell, Anne; Haslam, Stuart M Abstract: There is a critical need to develop small-molecule inhibitors of mucin-type O-linked glycosylation. The best-known reagent currently is benzyl-GalNAc, but it is effective only at millimolar concentrations. This article demonstrates that Ac5GalNTGc, a peracetylated C-2 sulfhydryl-substituted GalNAc, fulfills this unmet need. When added to cultured leukocytes, breast cells, and prostate cells, Ac5GalNTGc increased cell-surface VVA binding by ∼10-fold, indicating truncation of O-glycan biosynthesis. Cytometry, mass spectrometry, and western blot analysis of HL-60 promyelocytes demonstrated that 50-80 μM Ac5GalNTGc prevented elaboration of 30%-60% of the O-glycans beyond the Tn-antigen (GalNAcα1-Ser/Thr) stage. The effect of the compound on N-glycans and glycosphingolipids was small. Glycan inhibition induced by Ac5GalNTGc resulted in 50%-80% reduction in leukocyte sialyl-Lewis X expression and L-/P-selectin-mediated rolling under flow conditions. Ac5GalNTGc was pharmacologically active in mouse. It reduced neutrophil infiltration to sites of inflammation by ∼60%. Overall, Ac5GalNTGc may find diverse applications as a potent inhibitor of O-glycosylation 2021-01-01T00:00:00Z