Retro-1-Oligonucleotide Conjugates. Synthesis and Biological Evaluation

被引：5

作者：

Agramunt, Jordi ^{[1
,2
]}

Pedroso, Enrique ^{[1
,2
]}

Kreda, Silvia M. ^{[3
]}

Juliano, Rudolph L. ^{[4
]}

Grandas, Anna ^{[1
,2
]}

机构：

[1] Univ Barcelona, Dept Quim Inorgan & Organ, Secc Quim Organ, Marti i Franques 1-11, E-08028 Barcelona, Spain

[2] Univ Barcelona, IBUB, Fac Quim, Marti i Franques 1-11, E-08028 Barcelona, Spain

[3] Univ N Carolina, Sch Med, UNC Cyst Fibrosis Ctr, Chapel Hill, NC 27516 USA

[4] Univ N Carolina, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA

来源：

MOLECULES | 2019年 / 24卷 / 03期

关键词：

Retro-1; oligonucleotide conjugates; antisense; splice switching; SMALL MOLECULES; DELIVERY; ANTISENSE; OLIGONUCLEOTIDE; RETRO-1; INHIBITION; ENHANCE;

D O I：

10.3390/molecules24030579

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Addition of small molecule Retro-1 has been described to enhance antisense and splice switching oligonucleotides. With the aim of assessing the effect of covalently linking Retro-1 to the biologically active oligonucleotide, three different derivatives of Retro-1 were prepared that incorporated a phosphoramidite group, a thiol or a 1,3-diene, respectively. Retro-1-oligonucleotide conjugates were assembled both on-resin (coupling of the phosphoramidite) and from reactions in solution (Michael-type thiol-maleimide reaction and Diels-Alder cycloaddition). Splice switching assays with the resulting conjugates showed that they were active but that they provided little advantage over the unconjugated oligonucleotide in the well-known HeLa Luc705 reporter system.

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