Peptide and proteins with one or more beta-sheet strands exhibit the extraordinary ability to assemble into long fibrillar nanostructures via intermolecular hydrogen bonding. While designed alfa-helical proteins have been extensively studied, the design of beta-sheet structures remained a challenge for many year, because of their tendency to form unsoluble aggregates. The tendency to aggregate is manifested most clearly in nature in the formation of fibrils that follow upon extensive beta-sheet formations in proteins. The origin of the stability of beta-sheet folding has been attributed to interstrand hydrogen bonding and/or side chain hydrophobic interactions. Peptide models have proved valuable in probing the relationship between local sequence information and folded conformation in the absence of the tertiary interactions found in the native state of proteins, allowing intrinsic secondary structure propensities to be investigated in isolation. In synthetic model systems the turn/loop units are combined with peptide to form parallel or antiparallel ?-sheet. For reason of design and synthesis we report on antiparallel double strand. Several factors are of key importance including: (1) the nature and role of beta-turn in stabilizing dimeric structure formation, (2) propensities of different residues in the pre-organization of beta-strands, (3) the role of co-operativity in beta-sheet folding and stability, (4) insights into the nature of the stabilizing weak interactions. Recent studies revealed that the beta-turn sequence and its allowed geometry appears to be crucial in dictating the ?-strand alignment, and also that side chain interactions can have a significant stabilising effect on antiparallel double strand conformation. Here we centered the attention on sequences having high beta-sheet propensity.
SYNTHETIC MODEL SYSTEMS TO STUDY THE STRUCTURE AND INTERACTIONS OF POLYMERIC B-SHEETS
Fenude E;Saviano M
2017
Abstract
Peptide and proteins with one or more beta-sheet strands exhibit the extraordinary ability to assemble into long fibrillar nanostructures via intermolecular hydrogen bonding. While designed alfa-helical proteins have been extensively studied, the design of beta-sheet structures remained a challenge for many year, because of their tendency to form unsoluble aggregates. The tendency to aggregate is manifested most clearly in nature in the formation of fibrils that follow upon extensive beta-sheet formations in proteins. The origin of the stability of beta-sheet folding has been attributed to interstrand hydrogen bonding and/or side chain hydrophobic interactions. Peptide models have proved valuable in probing the relationship between local sequence information and folded conformation in the absence of the tertiary interactions found in the native state of proteins, allowing intrinsic secondary structure propensities to be investigated in isolation. In synthetic model systems the turn/loop units are combined with peptide to form parallel or antiparallel ?-sheet. For reason of design and synthesis we report on antiparallel double strand. Several factors are of key importance including: (1) the nature and role of beta-turn in stabilizing dimeric structure formation, (2) propensities of different residues in the pre-organization of beta-strands, (3) the role of co-operativity in beta-sheet folding and stability, (4) insights into the nature of the stabilizing weak interactions. Recent studies revealed that the beta-turn sequence and its allowed geometry appears to be crucial in dictating the ?-strand alignment, and also that side chain interactions can have a significant stabilising effect on antiparallel double strand conformation. Here we centered the attention on sequences having high beta-sheet propensity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
