Examination of the glycine and proline content of a wide range of elastomeric and amyloidogenic sequences revealed that a combined Pro/Gly proportion of (2P+G)=0,6 correlates with elastomeric assembly1. From a functional perspective, an increase in conformational order is generally associated with greater fiber stiffness. Increasing the spacing between proline residues significantly decreased the ability of polypeptide to reversibly self-associate. These data suggest that sequence elements and structural motifs play important roles in modulating alignment and assembly propensities and that precise regulation of proline/glycine composition is crucial for generating fibers with the required combination of elasticity and strength. Here we observe the conformational behaviour of D,L-alternating peptides containing proline and/or glycine in different position of the backbone. Hydrogen-bonding vs hydrophobic interactions: there are many occasions in the literature where conformational preference (propensity) is varied through hydrophobic interactions, even at the expense of hydrogen-bonds. The balance between hydrogen bonds and hydrophobic interactions is addressed to differing extents by existing molecular modelling packages. The relative importance of hydrophobic and polar interactions is especially important when attempting to predict the orientation of conformational behavior in the absence of experimental observations. The conformational behavior of D,L-alternating peptides clearly show the conformational changes due to feeble shift of the interactions equilibrium. Oligonorleucines, that on theoretical ground would prefer to form double stranded ?-helix, form instead an extended chain structure that is slightly arched (or has a shape of large incomplete ring). This contrast is due to the prevalence of hydrophobic interaction of the linear side chain (interdigitation) that stabilize the extended structure and is prevalent respect to the effect of hydrogen bonds in stabilize the helical structure. In our previous works2 we used two synthetic methods to balance H-bonds and hydrophobic interactions: (i) N-methylated residue in specific positions of the backbone was used to reduce the maximum number of H-bonds realizable and (ii) insertion of a bulky residue in central position of backbone in order to reduce hydrophobic interactions between side chains. In glycine-containing peptides we observe the influence of 'steric factor' in the stability of two conformations that coexists in equilibrium in chloroform solution.
Analysis of the Equilibrium of two Beta-Helical Structures
E Fenude
2020
Abstract
Examination of the glycine and proline content of a wide range of elastomeric and amyloidogenic sequences revealed that a combined Pro/Gly proportion of (2P+G)=0,6 correlates with elastomeric assembly1. From a functional perspective, an increase in conformational order is generally associated with greater fiber stiffness. Increasing the spacing between proline residues significantly decreased the ability of polypeptide to reversibly self-associate. These data suggest that sequence elements and structural motifs play important roles in modulating alignment and assembly propensities and that precise regulation of proline/glycine composition is crucial for generating fibers with the required combination of elasticity and strength. Here we observe the conformational behaviour of D,L-alternating peptides containing proline and/or glycine in different position of the backbone. Hydrogen-bonding vs hydrophobic interactions: there are many occasions in the literature where conformational preference (propensity) is varied through hydrophobic interactions, even at the expense of hydrogen-bonds. The balance between hydrogen bonds and hydrophobic interactions is addressed to differing extents by existing molecular modelling packages. The relative importance of hydrophobic and polar interactions is especially important when attempting to predict the orientation of conformational behavior in the absence of experimental observations. The conformational behavior of D,L-alternating peptides clearly show the conformational changes due to feeble shift of the interactions equilibrium. Oligonorleucines, that on theoretical ground would prefer to form double stranded ?-helix, form instead an extended chain structure that is slightly arched (or has a shape of large incomplete ring). This contrast is due to the prevalence of hydrophobic interaction of the linear side chain (interdigitation) that stabilize the extended structure and is prevalent respect to the effect of hydrogen bonds in stabilize the helical structure. In our previous works2 we used two synthetic methods to balance H-bonds and hydrophobic interactions: (i) N-methylated residue in specific positions of the backbone was used to reduce the maximum number of H-bonds realizable and (ii) insertion of a bulky residue in central position of backbone in order to reduce hydrophobic interactions between side chains. In glycine-containing peptides we observe the influence of 'steric factor' in the stability of two conformations that coexists in equilibrium in chloroform solution.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
