Self-assembling of peptides is tuned via an extended amphipathic helix.

Four peptides, C1 (spanning the helical segment of human neuropeptide Y from residue 15 to residue 29), C2 (spanning the helical segment of 21 to 31), C3 (the C-terminal fragment of neuropeptide Y involving residues 20 to 36) and P34-C3 (replacement of the glutamine with proline in position 34 of C3) were synthesized to study interaction between species. The information about the intermolecular interactions was extracted from their self-assembly behaviors. The results from CD and NMR showed that the addition of 2,2,2-trifluoroethanol (TFE) induces a stable amphipathic helix in each peptides and an extended helix was formed at the N-terminal of C1 and the C-terminal of C3. Pulsed field gradient NMR data revealed that C3 may undergo an enhanced interaction with TFE and a more favorable self-assembly as temperature was increased. In contrast, other three peptides were found to form larger size of oligomers at lower temperature and continuously dissociate into the monomeric form with increased temperature. Our results demonstrate that the self-assembly behavior may be tuned by the entropy and the energetics contributed by an extended helical conformation at terminus.

Dependence of peptide self-association on intermolecular interaction by PFGNMR in TFE aqueous solution: C-terminal analogues of NPY as model peptides.

We have investigated the dependence of peptide oligomerization on intermolecular interaction in terms of both energetic and structural effect by PFGNMR. Three peptides, NPY[20-36], Pro34-NPY[20-36] and NPY[21-31], which are related to human NPY, were synthesized as models in this work. In contrast to NPY[20-36], both Pro34-NPY[20-36] and NPY[21-31] were found with descendent affinity with TFE cluster and continuous dissociating with increased temperature. The observed results can be accounted by the entropic change with temperature and the varied hydrophobic interactions between species due to the differed structures of peptides from each other. The removal of helical secondary structure or residues from C-terminal region may increase the energetic difference between peptide-peptide self-associating and peptidesolvent binding. This increased energetic difference leads to larger dependence of association-dissociation equilibrium on temperature and entropic increase while dissociating.