Oligodeoxynucleotide conjugates

Wu, D., R. Boado, and W. Pardridge. 1996. Pharmacokinetics and blood-brain barrier transport of [3H]-biotinylated phosphorothioate oligodeoxynucleotide conjugated to a vector-mediated drug delivery system. J Pharmacol Exp Ther 276 206. 

Oishi M, Hayama T, Akiyama Y, Takae S, Harada A, Yamasaki Y, Nagatsugi F, Sasaki S, Nagasaki Y, Kataoka K (2005) Supramolecular assemblies for the cytoplasmic delivery of antisense oligodeoxynucleotide polylon complex (PIC) micelles based on polyethylene glycol)-S,S-oligodeoxynucleotide conjugate. Biomacromolecules 6 2449-2454... 

Mok H, Park JW, Park TG (2007) Antisense oligodeoxynucleotide-conjugated hyaluronic acid/protamine nanocomplexes for intracellular gene inhibition. Bioconjug Chem 18 1483-1489... 

Shea, R. G, Marsters, J C., and Bischofberger, N. (1990) Synthesis, hybridization properties and antiviral activity of lipid-oligodeoxynucleotide conjugates Nucl. Acids Res.lS, 3777-3783. 

Only after the oligodeoxynucleotide component of the conjugate was replaced with d(T)io could the adducts of external nucleophiles be observed. This alternative oligodeoxynucleotide was chosen based on the lack of detectable reaction between T and the parent ortho-QMS 1 Aqueous incubation of the d(T)10 QM conjugate in the absence and presence of 2-mercaptoethanol yielded the water and 2-mercaptoethanol adducts, respectively, as characterized by HPLC and mass spectroscopy.71... 

SCHEME 9.23 An oligodeoxynucleotide-bis(quinone methide) conjugate was designed for cross-linking duplex DNA by initial triplex formation but resulted at best in only monoalkylation of its target. 

Shirota, H. et al., Regulation of murine airway eosinophilia and Th2 cells by antigen-conjugated CpG oligodeoxynucleotides as a novel antigen-specific immunomodulator, J Immunol, 164, 5575, 2000. 

Avidin conjugates of oligodeoxynucleotides are hybrid molecules that not only provide multiple biotin binding sites, but can also be targeted to complimentary DNA or RNA sequences, by annealing interactions. Such conjugates are useful for the construction of macromolecular assemblies with a wide vari-... 

E.T. Rump, R.L. de Vrueh, L.A. Sliedregt, E.A. Biessen, T.J. van Berkel and M.K. Bijsterbosch, Preparation of conjugates of oligodeoxynucleotides and lipid structures and their interaction with low-density lipoprotein, Bioconjug. Chem. 9 (1998) 341-349. 

Roy et al. 1999). There are four basic DNA-based immunotherapeutic approaches immunization with DNA gene vaccines, allergen mixed with immu-nostimulatory oligodeoxynucleotide (ISS-ODN), allergen-ISS-ODN conjugates, and immunomodulation with ISS-ODN alone. ISS-ODN or CpG motifs provide Thl adjuvant activity for the immune response that developed toward the gene product (Sato et al. 1996). 

The demonstration that modificationsmay induce nuclease stability sufficient to enhance activity in cells in tissue culture and in animals has proved to be much more complicated because of the presence of 5 -exonucleases and -endonucleases. In our laboratory, 3 -modifi-cations and internal point modifications have not provided sufficient nuclease stability to demonstrate pharmacological activity in cells (183). In fact, even a 5-nucleotide-long phos-phodiester gap in the middle of a phosphoro-thioate oligonucleotide resulted in sufficient loss of nuclease resistance to cause complete loss of pharmacological activity (164). In mice, neither a 5 -cholesterol nor 5 -C18 amine conjugate altered the metabolic rate of a phospho-rothioate oligodeoxynucleotide in liver, kid-... 

A C-60 linked oligodeoxynucleotide has been demonstrated to facilitate sequence-specific modification of guanosine residues in a complementary oligonucleotide. The hybridisation of an oligonucleotide conjugated to Horse Radish Peroxidase can be directly measured as an electrical current which results from detection of the peroxide reaction upon hybridisation. ... 

Putta MR, Zhu FG, Wang D et al (2010) Peptide conjugation at the 5 -end of oligodeoxynucleotides abrogates Toll-like receptor 9-mediated immune stimulatory activity. Bioconjug Chem 21 39 5... 

---