Such scissors are an important part of the molecular biologist's tool kit. But there are only a handful of molecules known to have this ability.

Fig. 1: PMA-D-Phe. The molecular scissors all have a pyrenyl group (left) to act as the ‘blade’, and an amino acid (right) to anchor the scissors in place.

A Thai team led by Challa Kumar of the University of Connecticut, Storrs, and Apinya Buranaprapuk based at Connecticut and Bangkok's Srinakharinwirot University,1 made the scissors by joining two chemical units together with a short linking molecule.

On one side of the molecule lies a pyrenyl group, which sits snugly inside a pocket in the protein. On the other side is an amino acid—anchoring the scissors to the surface of the protein. The scientists tested three different scissor designs on two model proteins—lysozyme and bovine serum albumin (BSA).

The pyrenyl group absorbed light to trigger a series of atomic rearrangements, which cut the protein at a specific point along its backbone. A light-activated cutting reaction is much easier to control that one triggered by a chemical reagent, since switching the scissors on or off is as simple as flicking a switch. The pyrenyl group also produced a visible fluorescence, which changed depending on its binding to the protein, and is helpful for monitor how well it fits into its cavity.

The amino acid anchor can exist in two forms—enantiomers—which are mirror images of each other. The scientists hoped that scissors with a particular amino acid anchor would tend to cut proteins with a matching handedness.

The team found that their scissors were not very good at cutting BSA, but they were quite selective for one type of handedness over another—an effect that could be enhanced by fine-tuning the length of the linker in the scissors. One of the scissors was able to neatly snip lysozyme almost 60% of the time, although the two different enantiomers were not particularly selective, both snipping the protein in exactly the same place.

These results suggest that pyrenyl group's binding site is different from the reactive area of the protein which is snipped. This should help to fine-tune the scissor design to make it both selective and high-yielding.