Conjugates of Double-Stranded Oligonucleotides with Poly(ethylene glycol) and Keyhole Limpet Hemocyanin: A Model for Treating Systemic Lupus Erythematosus
Citations Over TimeTop 19% of 1994 papers
Abstract
Two types of oligonucleotides were synthesized with linker groups attached at the 5'-end. Both were repeating dimers of deoxyribocytidine and deoxyriboadenosine. A 20-mer was prepared with a thiol-containing linker, masked as a disulfide, and a 50-mer was prepared with a vicinal diol-containing linker. A tetraiodoacetylated poly(ethylene glycol) (PEG) derivative was synthesized and reacted with the thiol-containing 20-mer to provide an oligonucleotide PEG conjugate of precisely four oligonucleotides on each PEG carrier. The vicinal diol on the 50-mer was oxidized to an aldehyde and conjugated to keyhole limpet hemocyanin (KLH) to provide an oligonucleotide-KLH conjugate by reductive alkylation. The conjugates were annealed with complementary (TG)n strands. While the double-stranded oligonucleotide-KLH conjugate is an immunogen, eliciting the synthesis of antibodies against oligonucleotides, the PEG conjugate has the biological property of specifically suppressing (tolerizing) B cells which make antibodies against the immunizing oligonucleotide.
Related Papers
- → Phosphate Esters, Thiophosphate Esters and Metal Thiophosphates as Lubricant Additives(2013)121 cited
- → Thiophosphate and thiophosphonate analogues of glucose-1-phosphate: synthesis and enzymatic activity with a thymidylyltransferase(2013)15 cited
- → Inhibition of the phosphate-stimulated cytochromec oxidase activity by thiophosphate(1989)5 cited
- → The inhibitory effect of thiophosphate on the adenosine triphosphate-inorganic phosphate exchange reaction of rat liver mitochondria(1963)4 cited
- → ChemInform Abstract: The 4‐Oxopentyl Group as a Labile Phosphate/Thiophosphate Protecting Group for Synthetic Oligodeoxyribonucleotides.(2002)