A conformational α-helix to β-sheet transition accompanies racemic self-assembly of polylysine: an FT-IR spectroscopic study Original Research Article

The self-assembly of polylysine chains with opposite chiral senses is an intriguing phenomenon, suggesting that subtle hydrational effects may be a driving force of protein aggregation. We have used FT-IR spectroscopy to characterize the α-helix-to-β-sheet conformational transition that accompanies the aggregation of single and mixed enantiomers of polylysine. The preferential racemic self-assembly not only takes place at a lower temperature, but is also less prone to repulsive electrostatic interactions between lysine charged side chains, caused by decreasing pH (pD). While the process is generally irreversible, it yet appears to proceed in a stepwise manner through a sequence of thermodynamically, rather than kinetically controlled events involving gradual destabilization of α-helices. Interestingly, although the α/β-transition is in either case (single or mixed enantiomers) an endothermic process, it may also be induced by freezing of water, which leads to markedly more complete (and irreversible) aggregation of the mixed enantiomers. Relevance of these findings has been discussed in the context of protein aggregation studies.