title: Enhanced splice correction by 3', 5'-serinol and 2'-(ω-O-methylserinol) guarded OMe-RNA/DNA mixmers in cells.
abstract: Development of artificial nucleic acids for therapeutic applications warrants that the oligomers be endowed with high specificity, enzymatic stability and with no/reduced off-target effects. The balance between strength of the duplex with target RNA and enzyme stability is therefore the key factor for the designed modification. The chiral serinol derivative combines the attributes of amino- and methoxy- substitution when at 2'- position and at 3'- and 5'- ends, effectively balancing the duplex stability and resistance to hydrolytic enzymes. The biological effect seen is the remarkable improvement in splice correction by the steric blocking antisense oligonucleotide with just 4 modified units, i.e ~20% substitution with R-aminomethoxypropyloxy (R-AMP)-thymidine within the 2'-OMe 18mer sequence.
authors.affiliation: Organic Chemistry Division; CSIR-National Chemical Laboratory; Pune, India.
authors.forename: Venubabu
authors.initials: V
authors.lastname: Kotikam
authors.affiliation: Medical Research Council; Laboratory of Molecular Biology; Cambridge, UK.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Arzumanov
authors.affiliation: Medical Research Council; Laboratory of Molecular Biology; Cambridge, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gait
authors.affiliation: Organic Chemistry Division; CSIR-National Chemical Laboratory; Pune, India.
authors.forename: Vaijayanti A
authors.initials: VA
authors.lastname: Kumar
mesh_terms: D001483:Base Sequence; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D011412:Propanolamines / Q000737:chemistry*; D011409:Propylene Glycols / Q000737:chemistry*; D012313:RNA / Q000737:chemistry* / Q000235:genetics*; D012326:RNA Splicing; D012694:Serine / Q000737:chemistry; D013237:Stereoisomerism; D014529:Uridine / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D011412:Propanolamines; D011409:Propylene Glycols; C009182:ribothymidine; D012694:Serine; D012313:RNA; D004247:DNA; C072422:serinol; D014529:Uridine
keywords: antisense; oligonucleotides; splice correction; steric-blocking