Mechanism Of Short Amphiphilic Peptides Self-assembly

Molecular self-assembly is a common phenomenon in life system, and is one of the mostessential part of life science. In recent years, due to structural diversity and promisingapplication prospect in life science, peptide self-assembly has been extensively explored overthe past few decades. In this paper, we designed and synthesized several peptides based onAc-I3K-NH2: ImK, LmK (m=3-5) sets, XI2K set andDI3DK. We studied the effects ofhydrogen bonding, hydrophobic interaction and the molecular chirality on amphiphilicpeptide self-assembly. The main conclusions are listed as follows:We designed and synthesized three sets of short amphiphilic peptides (I3K, LI2K andL3K; L3K, L4K and L5K; I3K, I4K, and I5K) and investigated how I and L affected theirself-assembly in aqueous solution. The results have demonstrated a strong tendency of Igroups to promote the growth of β-sheet hydrogen bonding and the subsequent formation ofnanofibrillar shapes. All ImK (m=3-5) peptides assembled into nanofibers with consistentβ-sheet conformation, whereas the nanofiber diameters decreased as m increased due togeometrical constraint in peptide chain packing. In contrast, L groups have weak tendency topromote β-sheet structuring and their hydrophocity becomes dominant, resulting in globularmicelles in L3K assembly. However, increase in hydrophobic sequence to L5K inducedβ-sheet conformation due to the cooperative hydrophobic effect and the consequent formationof long nanofibers. The assembly of L4K was therefore intermediate between L3K and L5K,similar to the case of LI2K within the set of L3K, LI2K and I3K, with a steady transition fromthe dominance of hydrophobic interaction to hydrogen bonding.Compared the self-assembly of I3K and XI2K set, we have found that nomatter replacingIle by Leu, or substituteing NH by NCH3, all resulted in disruption of hydrogen bonding, andconsequently disruption of β-sheet conformation. Based on the I3K and I2LK, LI2Kcomparison, we have found that the substitution of Ile which is close to Lys is moredevastating for hydrogen bonding. However, due to the strong β-sheet tendency of Val, theself-assembly results of VI2K and I2VK didn’t show obvious differces. Our result has alsorevealed that if the peptide is so short like I2K that it will not be able to form hydrogenbonding interactions, not to mention stable nanostructures. Direct disruption of hydrogen bonding by substituteing NH for NCH3has great effect on the self-assembly of peptide.We conducted systematic study of structural dynamics ofLI3LK andDI3DK using circulardichroism under various temperatures. Our result has demonstrated thatDI3DK is not as stableasLI3LK at high temperature. We also have foundLI3LK andDI3DK form nanofibers with bothleft-handed helix and right-handed helix, which is very interesting but pitifully hard to explainat the moment.