"You can achieve the helical structure and the solubility but you have to design the helical structure in a very special way. The peptide design needs a very specific sequence. Then you're very limited in the type of polypeptide you can build, and it's not easy to design or handle these polypeptides," Cheng said.
In contrast, Cheng's group developed a very straightforward solution. Since the close proximity of the charges causes the repulsion that disrupts the helix, the researchers simply elongated the side chains, moving the charges farther from the backbone and giving them more freedom to keep their distance from one another.
The researchers observed that as they increased the length of the side chains with charges on the end, the polypeptides' propensity for forming helices also increased.
"It's such a simple idea move the charge away from the backbone," Cheng said. "It's not difficult at all to make the longer side chains, and it has amazing properties for winding up helical structures simply by pushing the distance between the charge and the backbone."
The group found that not only do polypeptides with long side chains form helices, they display remarkable stability even when compared to non-charged helices. The helices seem immune to temperature, pH, and other denaturing agents that would unwind most polypeptides.
This may explain why amino acids with large hydrophobic side chains are not found in nature. Such immutability would preclude dynamic winding and unwinding of protein structures, which is essential to many biological processes. However, rigid stability is a desirable trai
|Contact: Liz Ahlberg|
University of Illinois at Urbana-Champaign