Revisiting the Helical Cooperativity of Synthetic Polypeptides in Solution

Using synthetic polypeptides as a model system, the theories of helix–coil transition were developed into one of the most beautiful and fruitful subjects in macromolecular science. The classic models proposed by Schellman and Zimm–Bragg more than 50 years ago, differ in the assumption on whether the configuration of multiple helical sequences separated by random coil sections is allowed in a longer polypeptide chain. Zimm also calculated the critical chain lengths that facilitate such interrupted helices in different solvent conditions. The experimental validation of Zimm’s prediction, however, was not carefully examined at that time. Herein, we synthesize a series of homopolypeptide samples with different lengths, to systematically examine their helix–coil transition and folding cooperativity in solution. We find that for longer chains, polypeptides do exist as interrupted helices with scattered coil sections even in helicogenic solvent conditions, as predicted in the Zimm–Bragg model. The critical chain...