CONJUGATES OF DOUBLE-STRANDED OLIGONUCLEOTIDES WITH POLY(ETHYLENE GLYCOL) AND KEYHOLE LIMPET HEMOCYANIN - A MODEL FOR TREATING SYSTEMIC LUPUS-ERYTHEMATOSUS

Two types of oligonucleotides were synthesized with linker groups atta ched at the 5'-end. Both were repeating dimers of deoxyribocytidine an d deoxyriboadenosine. A 20-mer was prepared with a thiol-containing li nker, masked asa disulfide, and a 50-mer was prepared with a vicinal d iol-containing linker. A tetraiodoacetylated poly(ethylene glycol) (PE G) derivative was synthesized and reacted with the thiol-containing 20 -mer to provide an oligonucleotide PEG conjugate of precisely four oli gonucleotides on each PEG carrier. The vicinal diol on the 50-mer was oxidized to an aldehyde and conjugated to keyhole limpet hemocyanin (K LH) to provide an oligonucleotide-KLH conjugate by reductive alkylatio n. The conjugates were annealed with complementary (TG), strands. Whil e the double-stranded oligonucleotide-KLH conjugate is an immunogen, e liciting the synthesis of antibodies against oligonucleotides, the PEG conjugate has the biological property of specifically suppressing (to lerizing) B cells which make antibodies against the immunizing oligonu cleotide.