Morpholinos are six-membered rings that may provide higher conformational rigidity when incorporated into an oligonucleotide (ODN) backbone. Phosphorodiamidate morpholinos are chemically modified ODNs containing morpholinos in place of 2'-deoxyribose moieties throughout their backbone and have garnered much interest in recent years due to their ability to function as highly effective steric blockers in exon skipping therapy. To further explore the biophysical and biological properties of ODNs derived from morpholino nucleosides, we have replaced the 2'-deoxyribonucleotides of phosphodiester DNA with morpholinonucleotides to generate phosphoramidate ODNs.
View Article and Find Full Text PDFMajor hurdles associated with DNA-based biological applications include, among others, targeted cell delivery, undesirable nonspecific effects, toxicity associated with various analogues or the reagents used to deliver oligonucleotides to cells, and stability toward intracellular enzymes. Although a plethora of diverse analogues have been investigated, a versatile methodology that can systematically address these challenges has not been developed. In this contribution, we present a new, Clickable, and versatile chemistry that can be used to rapidly introduce diverse functionality for studying these various problems.
View Article and Find Full Text PDFThe major hurdle associated with utilizing oligodeoxyribonucleotides for therapeutic purposes is their poor delivery into cells coupled with high nuclease susceptibility. In an attempt to combine the nonionic nature and high nuclease stability of the P-C bond of methylphosphonates with the high membrane permeability, low toxicity, and improved gene silencing ability of borane phosphonates, we have focused our research on the relatively unexplored methylborane phosphine (Me-P-BH(3)) modification. This Article describes the automated solid-phase synthesis of mixed-backbone oligodeoxynucleotides (ODNs) consisting of methylborane phosphine and phosphate or thiophosphate linkages (16-mers).
View Article and Find Full Text PDFThe reactivity of (eta(3)-allyl)palladium chloro dimers [(1-R-eta(3)-C(3)H(4))PdCl](2) (R = H or Me) towards a sterically hindered diphosphazane ligand [EtN{P(OR)(2)}(2)] (R = C(6)H(3)(Pr(i))(2)-2,6), has been investigated under different reaction conditions. When the reaction is carried out using NH(4)PF(6) as the halide scavenger, the cationic complex [(1-R-eta(3)-C(3)H(4))Pd{EtN(P(OR)(2))(2)}]PF(6) (R = H or Me) is formed as the sole product. In the absence of NH(4)PF(6), the initially formed cationic complex, [(eta(3)-C(3)H(5))Pd{EtN(P(OR)(2))(2)}]Cl, is transformed into a mixture of chloro bridged complexes over a period of 4 days.
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