Synthesis of fluorophenyl ribonucleosides and their substitution into the U1A-U1snRNA complex

ORGN 515

Anne M. Baranger and Yulianingsih Benitex. Department of Chemistry, Wesleyan University, Hall-Atwater Laboratories, Lawn Avenue, Middletown, CT 06459
The RRM is a common RNA binding motif. The N-terminal RRM of the U1A spliceosomal protein binds stem loop 2 of U1snRNA with high affinity. The conserved aromatic residue Tyr13 participates in stacking interactions with C5 of stem loop 2. We are investigating the possible correlation between physical properties of aromatic base analogs and U1A:U1snRNA binding. We have synthesized a series of fluorophenyl ribonucleosides in which their quadrupole moment, hydrophobicity, and shape are varied. These analogs were substituted at C5. The oligonucleotides containing modified bases with the most negative and the most positive calculated quadrupole moment (phenyl ribonucleoside and pentafluorophenyl ribonucleoside, respectively) have similar affinity for U1A. Interestingly, the trifluorophenyl oligonucleotide binds 10-fold better to U1A than oligonucleotides containing phenyl and pentafluorophenyl. The trifluorophenyl oligonucleotide is less hydrophobic than pentafluorophenyl and has a near-neutral quadrupole moment. In contrast, we observed no binding of the 4-fluorophenyl oligonucleotide to U1A.