Synthesis and properties of polynucleotide recognition molecules

Micelles of Lipid−Oligonucleotide Conjugates: Implications for Membrane Anchoring and Base Pairing

“…Despite the large volume of the DNA headgroup and the possible attractive interactions between the dangling nucleic bases and the alkyl chains, lGeB gives micelles exhibiting a 10 nM upper limit of the critical micellar concentration (CMC). Studies on cholesterol conjugated 10mers reported either a 150 µM CMC 17 or no CMC at all below 1 mM. 18 This large difference with our CMC value can be interpreted as a consequence of the marked hydrophobic nature of the chalcone lipid used here.…”

“…Terminal lipophilic groups have variously been reported to decrease, ,, or have no effect at all 16,21 on stability of oligonucleotide duplexes. The T m variations were always small (less than 5 °C), and the present data are thus in line with previously published articles.…”

“…Such an issue is closely related to the improvement of the cellular uptake of antisense oligonucleotides by lipophilic modification. − According to this therapeutic strategy, short single-stranded DNA (ss-DNA) first bind to cellular membrane because of their hydrophobic moiety; then, after internalization, they hybridize to the targeted mRNA by sequence recognition and consequently prevent the translation of the associated protein. Oligonucleotides have been conjugated to numerous small lipophilic molecules including the widely used cholesterol, ,− alkyl chain, , di- o -alkyl- rac -glycerol, , fullerene, and adamantane . Biological effects such as inhibition of viral protein expression by lipid-conjugates could be observed on cell cultures, but the mechanisms ruling drug action are still unclear. , Indeed, cholesterol-DNA was found to bind to low-density lipoproteins receptors, allowing an alternative internalization route to passive membrane anchoring followed by pinocytosis .…”

“…Although lots of efforts have been devoted to lDNA synthesis and pharmaceutical characterization, data concerning the physicochemical properties of such amphiphiles are scarce. , Consequently, the present report investigates several features of newly synthesized lDNAs bearing a fluorescent label in their hydrophobic moiety. The manuscript first exposes the design and the syntheses of the fluorescent lDNAs.…”

“…[13][14][15] According to this therapeutic strategy, short single-stranded DNA (ss-DNA) first bind to cellular membrane because of their hydrophobic moiety; then, after internalization, they hybridize to the targeted mRNA by sequence recognition and consequently prevent the translation of the associated protein. Oligonucleotides have been conjugated to numerous small lipophilic molecules including the widely used cholesterol, 13,[16][17][18] alkyl chain, 16,19 di-o-alkyl-rac-glycerol, 15,16 fullerene, 20 and adamantane. 15 Biological effects such as inhibition of viral protein expression by lipid-conjugates could be observed on cell cultures, but the mechanisms ruling drug action are still unclear.…”