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Single strand targeted triplex formation: targeting purine-pyrimidine mixed sequences using abasic linkers
E R Kandimalla1, A N Manning, G Venkataraman
1Hybridon, Inc., Worcester, MA 01605, USA.
Nucleic Acids Research
|November 11, 1995
Summary
Foldback triplex-forming oligonucleotides (FTFOs) with an abasic linker (APD linker) show stable triplex formation. The APD linker maintains sequence specificity and can be incorporated without altering DNA triple helix geometry.
Area of Science:
- Biochemistry
- Molecular Biology
- Oligonucleotide Chemistry
Background:
- Foldback triplex-forming oligonucleotides (FTFOs) are crucial for targeted DNA interactions.
- Abasic linkers can be incorporated into oligonucleotides to modify their properties.
Purpose of the Study:
- To investigate the stability and sequence specificity of FTFOs containing a specific abasic linker (APD linker).
- To evaluate the impact of APD linker incorporation on triplex formation against C:G and T:A base pairs.
Main Methods:
- Synthesis and characterization of FTFOs with APD linkers.
- Assessment of triplex formation stability and sequence specificity.
- Molecular modeling studies to analyze structural impact and interactions.
Main Results:
- The APD linker exhibited less destabilization on C:G base pairs compared to T:A base pairs.
- Incorporation of multiple APD linkers decreased target binding but preserved sequence specificity in FTFOs.
- Molecular modeling confirmed APD linker compatibility with triple helix geometry and suggested potential hydrogen bonding interactions.
Conclusions:
- The APD linker is a viable modification for FTFOs, maintaining sequence specificity and structural integrity.
- The APD linker's impact on stability varies with the base pair context (C:G vs. T:A).
- Further studies can explore APD linker-modified FTFOs for therapeutic applications.