What is the difference in the effect of DTT (Dithiotreitol) and SDS (sodium dodecyl sulfate) for PAGE?
Proteins are thought of as long polyamide chains. This long chain of amino acids is known as the primary structure. Due to hydrogen bonding of the backbone amide groups, a protein chain will organise most of itself locally either as an &#x3b1;-helix or a &#x3b2;-sheet; which one depends on the angles to the &#x3b1; carbon. These secondary structure elements then cluster to form a tertiary structure in which hydrophobic residues typically cluster together, aromatic residues may form &#x3c0; stacks, positively and negatively charged residues come together to build up ionic interactions, cysteins come together in disulphide bridges and hydrogen bonds are also formed where applicable. This last step is repeated if a protein consists of multiple subunits to form the multi-protein complex’s quarternary structure.

Almost all of the structure elements I mentioned that explain tertiary structures are intermolecular, meaning that they do not constitute a chemical bond between the connected fragments. Therefore, these structure elements are easily broken by the action of SDS whose aliphatic chain inserts into these tertiary structures, interacts with them and practically captures them on its inside.

The only exception to the former paragraph are disulphide bridges between cysteins. These are actually a chemical bond conneting the two fragments. In a simplified reaction scheme, the synthesis of a disulphide bridge looks like this:

$$\ce{\underset{\text{cystein}}{2 R-S-H} -&gt;[][- 2e- \ -2 H+] \underset {\text{disulphide bridge}}{\ce{R-S-S-R}}}$$

Chemically, it is an oxidation of two cysteins.
Therefore, these disulphide bridges cannot be broken by the action of SDS alone. It takes a reductive agent such as DTT to resupply the electrons to reform the two cysteins. If no reducing agent is present (but there are disulphides in the protein structure), the disulphide bridge will remain intact and the protein will move not through the PA gel as it should according to its size since it is cyclic.