Oligonucleotides Can Adopt Large Numbers of Conformations in Solution
Our goal is to explain, as simply as possible, how single-stranded oligonucleotides become aptamers. Having explained the rotation or torsion angles in the sugar-phosphate backbone of nucleic acids, our next step is to examine backbone flexibility, starting with a 15-mer of poly-T.
Superposition of ten snapshots of single-stranded poly-T in solution.
Each of the ten models is represented by a straight line drawn through the atoms that comprise the backbone of the single-stranded DNA (ssDNA). The polydeoxynucleotide on the screen consists of 15 thymidine nucleotides linked together by 5′→3′ phosphodiester linkages. The full name is poly-thymidylic acid, which can be abbreviated as (pT)15 or simply poly-T.
As written, this polydeoxynucleotide has a phosphate group at the 5′ end and a free –OH at the 3′ end. Since thymine is the only base in poly-T, it exists as single-stranded molecule at all times. With "free" rotation around seven bonds per nucleotide unit, the sugar-phosphate backbone of poly-T can twist and curve into hundreds of different conformations.
The So-called "Random Coil" or Disordered State
Up to now we have looking at an ensemble of ten conformations of the 15-mer poly-T. However, the 15-mer can adopt hundreds of other conformations without steric clashes.
Let's look at two of these conformations as space-filling models:
Question: Which of these two models is more stable? Explain your reasoning.
Despite close packing of the atoms along the backbone, the sugar-phosphate backbone is amazingly flexible. Without this flexibility, base stacking in aptamers, as well as in the double helices and other important DNA and RNA structures, would be impossible.