Synthesis of Janus compounds for the recognition of G-U mismatched nucleobase pairs.

Abstract

The design and synthesis of two Janus-type heterocycles with the capacity to simultaneously recognize guanine and uracyl in G-U mismatched pairs through complementary hydrogen bond pairing is described. Both compounds were conveniently functionalized with a carboxylic function and efficiently attached to a tripeptide sequence by using solid-phase methodologies. Ligands based on the derivatization of such Janus compounds with a small aminoglycoside, neamine, and its guanidinylated analogue have been synthesized, and their interaction with Tau RNA has been investigated by using several biophysical techniques, including UV-monitored melting curves, fluorescence titration experiments, and (1)H NMR. The overall results indicated that Janus-neamine/guanidinoneamine showed some preference for the +3 mutated RNA sequence associated with the development of some tauopathies, although preliminary NMR studies have not confirmed binding to G-U pairs. Moreover, a good correlation has been found between the RNA binding affinity of such Janus-containing ligands and their ability to stabilize this secondary structure upon complexation.

• Authors: Gerard Artigas, Vicente Marchán
• Journal: The Journal of organic chemistry (J Org Chem) Vol. 78 Issue 21 Pg. 10666-77 (Nov 01 2013) ISSN: 1520-6904 [Electronic] United States
• PMID: 24087986 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ligands
• Uracil
• Guanine
• RNA

Topics

• Base Pair Mismatch
• Base Pairing
• Circular Dichroism
• Guanine (chemistry)
• Hydrogen Bonding
• Ligands
• Magnetic Resonance Spectroscopy
• Nucleic Acid Conformation
• RNA (chemistry)
• Thermodynamics
• Uracil (chemistry)