Theresa Devlin

Acyloxyaryl prodrugs of oligonucleoside phosphorothioates

Abstract Improved design, synthesis, and evaluation of an oligonucleotide prodrug is described.

N-pent-4-enoyl (PNT) group as a universal nucleobase protector: Applications in the rapid and facile synthesis of oligonucleotides, analogs, and conjugates

Abstract Rapid synthesis of phosphoric diester and phosphorothioate oligonucleotides in 1 micromol to 1 millimol scale has been achieved using PNT nucleoside phosphoramidites. Furthermore, facile synthesis of mixed backbone oligonucleotides (MBOs) as antisense agents can be carried out using PNT nucleoside phosphoramidites in conjunction with PNT nucleoside H -phosphonates and PNT nucleoside phosphonamidites. The versatility of the PNT group is further demonstrated by its use in the preparation of bioreversible oligonucleotide conjugates.

Oligonucleoside phosphoramidates from N-pent-4-enoyl nucleoside H-phosphonates

Abstract N -pent-4-enoyl nucleoside H -phosphonates are versatile building blocks for the synthesis of oligonucleotide phosphoramidates.

Mixed backbone oligonucleotides containing internucleotidic primary phosphoramidate linkages

Abstract Mixed backbone oligonucleotides (MBOs) which contain segments of primary phosphoramidate linkages (PO-NH 2 ) in conjunction with either phosphoric diesters (PO), or phosphorothioates (PS) were prepared. Thermal denaturation of the duplexes with RNA and DNA reveal that they form stable duplexes which display cooperative melting profiles. Preliminary stability studies reveal that the PO-NH 2 linkage is resistant to serum nucleases. Thus, these MBOs represent novel antisense molecules.

N-pent-4-enoyl nucleosides: Application in the synthesis of support-bound and free oligonucleotide analogs by the H-phosphonate approach

Abstract N-pent-4-enoyl nucleoside H-phosphonates are versatile building blocks for the synthesis of support-bound and free oligonucleotide analogs.

Improved synthesis of oligonucleoside methylphosphonate analogs

Abstract Solid-phase synthesis using pent-4-enoyl nucleoside PNT phosphonamidites allow for the facile preparation of oligonucleoside methylphosphonates, methylphosphonothioates and their chimeric analogs. With PNT phosphonamidites, nucleobase and phosphate deprotection, as well as, cleavage from the support can all be accomplished by treatment of the support-bound oligonucleotide with NH 4 OH (28%, rt, 1 h).

Synthesis, Biophysical Properties, and Stability Studies of Mixed Backbone Oligonucleotides Containing Novel Non-Ionic Linkages

Abstract Mixed backbone oligonucleotides (MBOs) (containing ionic and non-ionic internucleotidic linkages) in which the non-ionic segments are either methylphosphotriester (PO-OMe) or primary phosphoramidate (PO-NH2) linkages have been prepared using the recently described N-pent-4-enoyl (PNT) nucleoside phosphoramidates and H-phosphonates. Biophysical properties and stability studies suggest that these MBOs are novel antisense molecules.