Synthesis and biological evaluation of sialyl-oligonucleotide conjugates targeting leukocyte B trans-membranal receptor CD22 as delivery agents for nucleic acid drugs. Issue 11 (1st June 2016)

• Record Type: Journal Article
• Authors: St-Pierre, Gabrielle; Pal, Sudip; Østergaard, Michael E.; Zhou, Tianyuan; Yu, Jinghua; Tanowitz, Michael; Seth, Punit P.; Hanessian, Stephen
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 11(2016)
• Page Start: 2397
• Page End: 2409
• Publication Date: 2016-06-01
• Subjects: CD22 -- Sialosides -- Multivalency -- Antisense -- Conjugation; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.03.047
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Antisense oligonucleotides (ASOs) modified with ligands which target cell surface receptors have the potential to significantly improve potency in the target tissue. This has recently been demonstrated using triantennary N -acetyld -galactosamine conjugated ASOs. CD22 is a cell surface receptor expressed exclusively on B cells thus presenting an attractive target for B cell specific delivery of drugs. Herein, we reported the synthesis of monovalent and trivalent ASO conjugates with biphenylcarbonyl (BPC) modified sialic acids and their study as ASO delivery agents into B cells. CD22 positive cells exhibited reduced potency when treated with ligand modified ASOs and mechanistic examination suggested reduced uptake into cells potentially as a result of sequestration of ASO by other cell-surface proteins.