Revision as of 01:26, 9 October 2021

pH-sensitive DNA switch

A pH-sensitive DNA nanoswitch, which folds into triplex under low pH and duplex under high pH.

Background & Mechanism

Conventional base-pairing present in DNA between A-T and C-G are known as Watson-Crick base pairing denoted as "-", also known as complementary base pairing. However, another type of pairing exists as well, known as Hoogsteen base pairing. One of the bases of A-T or C-G is flipped, and hydrogen bonds hold them together as well. However, C·G hoogsteen bonds (denoted as "·")require protonation of Cytosine to form one essential hydrogen bond.

Figure 1 Watson-Crick& Hoogsteen base pairing.^[1] Re-illustrated by Anthea.

Thus, a DNA switch can be designed to be pH-sensitive. As shown in Figure 2, the DNA can fold into a triplex under low pH, and unfold into a duplex at high pH. Due to the protonation of cytosine to form C·G bonds, regulating the amount of C·G and A·T present in the switch could regulate its threshold value of folding.

Figure 2^[2] A DNA nanoswitch, that folds in different pH ranges depending on its proportion of C·G and A·T pairs.

Part Info

BBa_K3897000 is a triplex switch design in previous literature^[2], with T·A bonds at 60%. The switch consists of 4 protonations sites and is connected by short sequences. It shows the greatest change in folding. Between pH 6-7 which suits the pH difference between normal tissue cells (pH7.1) and tumor tissues (pH 6.5).

Figure 3 The folding of TAT60 DNA switch according to literature^[3].