Interactions of oligonucleotide analogs containing methylphosphonate internucleotide linkages and 2′-O-methylribonucleosides

Abstract

ABSTRACT

Antisense Medicinal Chemistry

“…It is well established that Me-phosphonate-modified DNA hybridizes weakly to complementary sequences (KEAN et al 1994;REYNOLDS et al 1996). Use of the more stable Me-phosphonate Rp stereoisomer provides increased binding compared with racemic Me-phosphonates.…”

Consequences of P‐Chirality in Chimeric 2′‐O‐Methyloligoribonucleotides with Stereoregular Methylphosphonothioate Linkages

“…The unusual differences in the affinity of stereoregular chimeric 2Ј-O-methyloligoribonucleotides towards DNA and RNA templates is discussed in the context of the predominant conformations of these hybrid duplexes and possible different solvation patterns. [38,39] …”

“…The thermodynamic properties of the duplexes formed by stereoregular chimeric oligonucleotides 2 strongly depend on the nature of the template. 2Ј-O-Methyloligoribonucleotides are considered as structural analogues of RNA with a C3Ј-endo pucker [32,38] and therefore possess an increased affinity towards RNA templates. [34,36] Note that in the case of a single P-chiral modification incorporated into the middle of Oligo-MePS [(R P )-2c and (S P )-2d], the difference in stability caused by the opposite absolute configuration [(R P )-2c/ DNA vs. (S P )-2d/DNA] is ∆T m = 12.4°C for DNA template 9, and ∆T m = 5°C for duplexes (R P )-2c/RNA and (S P )-2d/RNA.…”

A novel sequence-specific RNA quantification method using nicking endonuclease, dual-labeled fluorescent DNA probe, and conformation-interchangeable oligo-DNA

“…Currently, the activity (catalytic rate) of Nb.BbvC I is one of the rate-limiting factors in the L-assay, and thus development of a high-activity nicking endonuclease (Cherry et al 1999;Bellamy et al 2005;Zheng and Roberts 2007) is expected to increase the reaction rate, resulting in more sensitive quantification. Moreover, improvement of the conformation (sequence design) or chemical modification of the L-DNA may reduce BS by the L-DNA (Kean et al 1994). Indeed, L-DNA with a 3-nt loop resulted in less BS than that with a 4-nt loop (Table 2,Conditions 15,18).…”