Peptide-oligonucleotide conjugates

Marchan, V., Ortega, S., Pulido, D., Pedroso, E., and Grandas, A. (2006) Diels-Alder cycloadditions in water for the straightforward preparation of peptide-oligonucleotide conjugates. Nucleic Acids Res. 34(3), e24. 

The stepwise synthesis of peptide-oligonucleotide conjugates has been re-ported. The synthesis makes use of (+)-3-amino-1,2-propanediol which is tethered to a solid support through the central hydroxyl group, with Fmoc... 

C) or 20% piperidine in DMF (3 h, ambient temperature) the 3 -phosphate can be liberated from NPE support by standard ammonia treatment. The NPE linker has been used primarily for the preparation of the oligonucleotides containing sensitive nucleobases [234], with DBU-mediated deprotection and phosphoramidite or H-phosphonate chemistry, [235] as well as for the synthesis of peptide-oligonucleotide conjugates [236]. 

A similar Fmoc-inspired anchor [237] (Figure 19.7) has also been applied for oligonucleotide synthesis following its success in peptide chemistry, for example, for the preparation of oligonudeotides via the NPE scheme [218] and the synthesis of peptide-oligonucleotide conjugates [238],... 

A more hydrophilic version of a disulfide support has been developed by Bonfils and Thuong [294] who synthesized a polymer with a a),(o -dithiodi- 2-[2-(2-ethoxy)ethoxy]ethyl linker (Figure 19.13). The support performed similarly to those described above [267, 268, 293], and the heterobifunctional oligonucleotides obtained have been used for the preparation of peptide-oligonucleotide conjugates [296],... 

There is considerable interest in the synthesis of peptide-oligonucleotide conjugates. 

Astriab-Fisher A, Sergueev DS, Fisher M, Shaw BR, Juliano RL. Antisense inhibition of P-glycoprotein expression using peptide-oligonucleotide conjugates. Biochem Pharmacol 2000 60 83-90. 

A series of peptide-oligonucleotide conjugates (POCs) were prq)ared and analyzed on a PRP-1 column (A = 258nm). A 60-min 100/0->40/60 water (0.1 M triethylanunonium acetate at pH 9.7)/acetonitriIe gradient was used. Peaks such as unreacted DNA, FMOC-( Om),2-Cys(NH2)-DNA, and ( Om)3-Cys(NH2)2-DNA were separated. Eight products were produced and identified... 

Despite some hmitations, maleimides were successfully applied in the field many times, including in the labeling of diene-containing nucleic acids [74, 75], for labeling and immobilizing proteins [76] and for the preparation of peptide-oligonucleotide conjugates [77]. 

Marchan V, Ortega S, Pulido D, Pedroso E, Grandas A (2006) Synthesis of peptide-oligonucleotide conjugates by Diels-Alder cycloaddition in water. Nucleic Acids Res 34(3) e24... 

Mier W, Eritja R, Mohammed A, Haberkom U, Eisenhut M. Preparation and evaluation of tumor-targeting peptide-oligonucleotide conjugates. Bioconjug Chem 2000 11 855-860. 

Pagels, P., Starke, D., Kramer, W., Hepatobiliary transport of bile add amino add, bile add peptide, and bile acid oligonucleotide conjugates in rats, Hepatology 1999, 30, 1257-1268. 

Bongartz, J.P., Aubertin, A.M., Milhaud, P.G., Lebleu, B. (1994). Improved biological activity of antisense oligonucleotides conjugated to a fusogenic peptide. Nucleic Acids Res., 22, 4681 1688. 

Oligonucleotide analogues have commonly been considered as nucleic acids even in the absence of an acidic group, e.g., methyl phosphon-ates. In a formal sense, peptide nucleic acids are neither peptides nor composed of nucleic acids, nor should they be confused with peptide/protein oligonucleotide conjugates as described in the previous section. The PNA monomeric unit contains features of both amino acids and nucleosides. The four common base portions of nucleosides—adenyl, cytosyl, guanidyl, and thymidyl—are tethered to the PNA backbone, which carries the functionality of common amino acids. Amide bonds then consecutively link these monomer units. The term polyamide is more chemically appropriate thus an alternative name is polyamide nucleoside analogue, which is still abbreviated PNA. 

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