Abstract
In further study of our series of six-membered ring-containing nucleic acids, different 1',3'-di-O-methyl altropyranoside nucleoside analogs (DMANA) were synthesized comprising all four base moieties, adenine, cytosine, uracil and guanine. Following assembly into oligonucleotides (ONs), their affinity for natural oligonucleotides was evaluated by thermal denaturation of the respective duplexes. Data were compared with results obtained previously for both anhydrohexitol (HNAs) and 3'-O-methylated altrohexitol modified ONs (MANAs). We hereby demonstrate that ONs modified with DMANA monomers, unlike some of our previously described analogues with constrained 6-membered hexitol rings, did not improve thermodynamic stability of dsRNA complexes, most probably in view of an energetic penalty when forced in the required 1C4 pairing conformation. Overall, a single incorporation was more or less tolerated or even positive for the adenine congener, but incorporation of a second modification afforded a slight destabilization (except for A), while a fully modified sequence displayed a thermal stability of -0.3 °C per modification. The selectivity of pairing remained very high, and the new modification upon incorporation into a DNA strand, s...Continue Reading
References
Nov 24, 1994·Nature·R W Wagner
Feb 25, 2000·Biochemical Pharmacology·M VandermeerenP Herdewijn
May 12, 2000·Biochimica Et Biophysica Acta·P Herdewijn
Sep 13, 2000·Antisense & Nucleic Acid Drug Development·P Herdewijn
Oct 16, 2001·Nucleic Acids Research·A Van AerschotP Herdewijn
Jul 18, 2002·Nature Reviews. Drug Discovery·Joanna B Opalinska, Alan M Gewirtz
Dec 10, 2003·Oncogene·Nicholas M Dean, C Frank Bennett
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Nov 13, 2004·Nature·Jürgen SoutschekHans-Peter Vornlocher
Nov 24, 2004·Current Opinion in Chemical Biology·Muthiah Manoharan
Feb 1, 2007·Nucleic Acids Research·Michael FisherPiet Herdewijn
Jun 2, 2007·Nature Reviews. Drug Discovery·Antonin de FougerollesJudy Lieberman
May 16, 2008·Carbohydrate Research·K TesteY Champavier
Apr 21, 2009·European Journal of Pharmacology·Michael FisherPiet Herdewijn
Sep 10, 2009·Chemistry : a European Journal·Daniele D'AlonzoPiet Herdewijn
Nov 26, 2009·Carbohydrate Research·R LucasM Guilloton
Mar 17, 2010·Chemistry & Biodiversity·Rakesh N Veedu, Jesper Wengel
Sep 1, 2011·RNA·Blaine H M Mooers, Amritanshu Singh
Apr 21, 2012·Science·Vitor B PinheiroPhilipp Holliger
Aug 2, 2012·Expert Opinion on Biological Therapy·Wei-Qiong Yang, Yi Zhang
Oct 12, 2012·Molecular Diversity·G ChatelainArthur Van Aerschot
Mar 8, 2013·Nature Medicine·Kevin Jiang
Mar 13, 2014·Molecular Therapy. Nucleic Acids·Qi-Long LuTerence Partridge
Jun 24, 2014·Protein & Cell·Shan GaoHui Wang
Aug 6, 2014·Molecular Therapy. Nucleic Acids·Hongguang SunYouli Zu
Sep 5, 2014·Current Opinion in Oncology·Daniela Castanotto, Cy A Stein
Dec 4, 2014·Nature·Alexander I TaylorPhilipp Holliger