کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5217856 | 1383309 | 2013 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis and properties of 2â²-O-[R- and S-(2-amino-3-methoxy)propyl] (R-AMP and S-AMP) nucleic acids Synthesis and properties of 2â²-O-[R- and S-(2-amino-3-methoxy)propyl] (R-AMP and S-AMP) nucleic acids](/preview/png/5217856.png)
Substitution at 2â²-position by either amino- or methoxy-pendant groups of the antisense oligonucleotides (AONs) is known to enhance their therapeutic value. A simple modification is described here in which we introduce both these groups in the form of enantiospecific tethers at 2â²-position. Practical synthesis of modified nucleosides using natural l-serine, en route to R-AMP- and S-AMP-AONs is presented. Such tethered ONs formed stable DNA:RNA duplexes and the stability was found to be marginally better than the methoxyethyl/methoxypropyl-substituted MOE/MOP-AONs. The stereochemistry of the tether effectively differentiated the hydrolytic cleavage of AONs and the R-AMP-AON was three times more stable than the S-AMP-AONs after 4Â h. In comparison, the MOE- or MOP-AONs were almost completely digested by SVPD after 1Â h.
Journal: Tetrahedron - Volume 69, Issue 31, 5 August 2013, Pages 6404-6408