title: Synthesis, Thermal Stability, Biophysical Properties, and Molecular Modeling of Oligonucleotides of RNA Containing 2'-O-2-Thiophenylmethyl Groups.
abstract: Dodecamers of RNA [CUACGGAAUCAU] were functionalized with C2'-O-2-thiophenylmethyl groups to obtain oligonucleotides 10-14 and 17. The modified nucleotides were incorporated into RNA strands via solid-phase synthesis. The biophysical properties of these ONs were used to quantify the effects of this modification on RNA:RNA and RNA:DNA duplexes. A combination of UV-vis and circular dichroism were used to determine thermal stabilities of all strands, which hybridized into A-form geometries. Destabilization of the double stranded RNA was measured as a function of number of consecutive modifications, reflected in decreased thermal denaturation values (ΔTm, ca. 2.5-11.5 °C). Van't Hoff plots on a duplex containing one modification (10:15) displayed a ca. ΔΔG° of +4 kcal/mol with respect to its canonical analogue. Interestingly, hybridization of two modified strands (13:17, containing a total of eight modifications) resulted in increased stability and a distinct secondary structure, reflected in its CD spectrum. Molecular modeling based on DFT calculations shed light on the nature of this stability, with induced changes in the torsional angle δ (C5'-C4'-C3'-O3) and phosphate-phosphate distances that are in agreement with a compacted structure. The described synthetic methodology and structural information will be useful in the design of thermodynamically stable structures containing chemically reactive modifications.
authors: Department of Chemistry, University of Colorado Denver , Science Building 1151 Arapahoe Street, Denver, Colorado 80204, United States.
authors: Joseph C
authors: JC
authors: Nguyen
authors: Department of Chemistry, University of Colorado Denver , Science Building 1151 Arapahoe Street, Denver, Colorado 80204, United States.
authors: Yannick Kokouvi
authors: YK
authors: Dzowo
authors: Department of Chemistry, University of Colorado Denver , Science Building 1151 Arapahoe Street, Denver, Colorado 80204, United States.
authors: Carly
authors: C
authors: Wolfbrandt
authors: Department of Chemistry, University of Colorado Denver , Science Building 1151 Arapahoe Street, Denver, Colorado 80204, United States.
authors: Justin
authors: J
authors: Townsend
authors: Department of Chemistry, University of Colorado Denver , Science Building 1151 Arapahoe Street, Denver, Colorado 80204, United States.
authors: Stanislav
authors: S
authors: Kukatin
authors: Department of Chemistry, University of Colorado Denver , Science Building 1151 Arapahoe Street, Denver, Colorado 80204, United States.
authors: Haobin
authors: H
authors: Wang
authors: Department of Chemistry, University of Colorado Denver , Science Building 1151 Arapahoe Street, Denver, Colorado 80204, United States.
authors: Marino J E
authors: MJ
authors: Resendiz