NMR study of the structure and self-association of core peptide in aqueous solution and DPC micelles.

Core peptide is a hydrophobic peptide derived from the T-cell antigen receptor-alpha chain (TCR-α) transmembrane region with therapeutic potential. The mechanism by which the peptide inserts into the membrane, including any requirements to change conformational or association states during the insertion, is unclear. Here, the self-association and secondary structure of Core peptide in aqueous solution and in dodecylphosphocholine (DPC) micelles were examined using various nuclear magnetic resonance (NMR) techniques. NMR diffusion measurements were performed on 0.05, 1, and 5 mM Core peptide in Dâ‚‚O. These samples had pH values varying from 3 to 4. A constant measured diffusion coefficient of ~2 X 10â»Ã‚¹Ⱐm²sâ»Ã‚¹ was observed in these samples indicating that Core peptide was monomeric. Multidimensional NMR experiments (i.e., TOCSY and NOESY) revealed the formation of β-strands in water at low pH and random coil in DPC micelles. The results of this study reveal that at relatively low pH, the insertion mechanism must involve Core peptide in the monomeric state but it undergoes a conformational transition during membrane insertion.