Formation of Annular Protofibrillar Assembly by Cysteine Tripeptide: Unravelling the Interactions with NMR, FTIR and Molecular Dynamics.
Related Articles Formation of Annular Protofibrillar Assembly by Cysteine Tripeptide: Unravelling the Interactions with NMR, FTIR and Molecular Dynamics.
J Phys Chem B. 2017 Jun 08;:
Authors: Banerji B, Chatterjee M, Pal U, Maiti NC
Abstract
Both the hydrogen bonding and hydrophobic interactions play a significant role in molecular assembly including self assembly of proteins and peptides. In this investigation, we reported formation of annular protofibrillar structure (diameter ~500 nm) made of a newly synthesized s-benzyl-protected cysteine tripeptide which was primarily stabilized by hydrogen bonding and hydrophobic interactions. AFM and FESEM analyses found small oligomers (~ 60 nm in diameter) to bigger annular (~ 300 nm) with an inner diameter of 100 nm and protofibrillar structure after 1-2 days incubation. ROESY NMR spectral analysis revealed the presence of several non-bonded proton-proton interactions among the residues; such as amide protons with methylene group, aromatic protons with tertiary butyl group, methylene protons with the tertiary butyl group etc. These added significant stabilization to bring the peptides closer to form a well ordered assembled structure. H/D exchange NMR measurement further suggested that two individual amide protons among the three amide groups were strongly engaged with the adjacent tripeptide via H-bond interaction. However, the remaining amide proton was found to be exposed to solvent and remained non-interacting with the other tripeptide molecules. In addition to chemical shift values, a significant change in amide bond vibrations of the tripeptide was found due to self assembly formation. The amide I mode of vibrations involving two amide linkages appeared at 1641 cm-1 and 1695 cm-1 in the solid state. However, in the assembled state the stretching band at 1695 cm-1 became broad and slightly shifted to ~1689 cm-1. On the contrary, the band at 1641 cm-1 shifted to 1659 cm-1 and indicated that the -C=O bond associated with this vibration became stronger in the assembled state. These changes in FTIR frequency clearly indicated changes in amide backbone conformation and associated hydrogen bonding pattern due to formation of the assembled structure. In addition to hydrogen bonding, molecular dynamics simulation indicated that the number of ?-? interactions also increased with increasing the number of tripeptide participated in the self assembly process. Combined results envisaged a cross ?-sheet assembly unit consisted of four intermolecular hydrogen bonds. Such non-covalent peptide assemblies glued by hydrogen bonding and other weak forces may be useful in developing nano-capsule and related materials.
PMID: 28593765 [PubMed - as supplied by publisher]
More...