Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Nycholat, CM; Duan, S; Knuplez, E; Worth, C; Elich, M; Yao, A; O'Sullivan, J; McBride, R; Wei, Y; Fernandes, SM; Zhu, Z; Schnaar, RL; Bochner, BS; Paulson, JC.
A Sulfonamide Sialoside Analogue for Targeting Siglec-8 and -F on Immune Cells.
J Am Chem Soc. 2019; 141(36):14032-14037
Doi: 10.1021/jacs.9b05769
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- Abstract:
- The Siglec family of cell surface receptors have emerged as attractive targets for cell-directed therapies due to their restricted expression on immune cells, endocytic properties, and ability to modulate receptor signaling. Human Siglec-8, for instance, has been identified as a therapeutic target for the treatment of eosinophil and mast cell disorders. A promising strategy to target Siglecs involves the use of liposomal nanoparticles with a multivalent display of Siglec ligands. A key challenge for this approach is the identification of a high affinity ligand for the target Siglec. Here, we report the development of a ligand of Siglec-8 and its closest murine functional orthologue Siglec-F that is capable of targeting liposomes to cells expressing Siglec-8 or -F. A glycan microarray library of synthetic 9-N-sulfonyl sialoside analogues was screened to identify potential lead compounds. The best ligand, 9-N-(2-naphthyl-sulfonyl)-Neu5Acα2-3-[6-O-sulfo]-Galβ1-4GlcNAc (6'-O-sulfo NSANeu5Ac) combined the lead 2-naphthyl sulfonyl C-9 substituent with the preferred sulfated scaffold. The ligand 6'-O-sulfo NSANeu5Ac was conjugated to lipids for display on liposomes to evaluate targeted delivery to cells. Targeted liposomes showed strong in vitro binding/uptake and selectivity to cells expressing Siglec-8 or -F and, when administered to mice, exhibit in vivo targeting to Siglec-F+ eosinophils.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Antigens, CD - metabolism
- Antigens, Differentiation, B-Lymphocyte - metabolism
- Antigens, Differentiation, Myelomonocytic - metabolism
- B-Lymphocytes - drug effects, metabolism
- CHO Cells - administration & dosage
- Cricetulus - administration & dosage
- Humans - administration & dosage
- Lectins - antagonists & inhibitors, metabolism
- Liposomes - chemistry, metabolism
- Mice - administration & dosage
- Molecular Conformation - administration & dosage
- Sialic Acid Binding Immunoglobulin-like Lectins - administration & dosage
- Sialic Acids - chemistry, pharmacology
- Sulfonamides - chemistry, pharmacology
- T-Lymphocytes - drug effects, metabolism