Triple helix formation by alpha-oligodeoxynucleotides: a vibrational spectroscopy and molecular modeling study

Area of Science:

• Structural Biology
• Biophysics
• Molecular Genetics

Background:

• DNA triple helices are crucial nucleic acid structures with diverse biological roles.
• Understanding their precise 3D structures, including sugar pucker and strand orientation, is key to elucidating function.
• Previous studies have suggested variations in triplex structures, necessitating detailed investigation.

Purpose of the Study:

• To elucidate the sugar conformations within various DNA triple helices.
• To determine the hydrogen bonding schemes and polarities of the third strand in these triplexes.
• To differentiate structural characteristics between alpha and beta DNA-RNA triplexes.

Main Methods:

• Fourier transform infrared spectroscopy (FTIR)
• Raman spectroscopy
• Molecular mechanics calculations
• Vibrational spectroscopy

Main Results:

• Identified exclusively S-type sugar conformations in the alpha dT12.beta dAn.beta dTn triple helix.
• Detected both S- and N-type sugar markers in alpha dC12+.beta dGn.beta dCn spectra.
• Proposed third strand hydrogen-bonding schemes and polarities based on spectroscopic constraints.
• Determined the third strand is parallel to the purine strand in alpha dT12.beta dA12.beta dT12 via reverse Hoogsteen bonds.
• Found the third strand to be antiparallel to the purine strand in alpha dC12+.beta dG12.beta dC12 via Hoogsteen bonds.

Conclusions:

• Spectroscopic and computational data reveal distinct sugar conformations and hydrogen bonding patterns in DNA triple helices.
• Structural differences, particularly strand polarity and sugar pucker, are evident between different triplex compositions.
• These findings provide a refined structural model for DNA triple helices, contributing to the understanding of their stability and interactions.