Stability Of Helical Conformation Research Articles

N-terminal diproline and charge group effects on the stabilization of helical conformation in alanine-based short peptides: CD studies with water and methanol as solvent.

Protein folding problem remains a formidable challenge as main chain, side chain and solvent interactions remain entangled and have been difficult to resolve. Alanine-based short peptides are promising models to dissect protein folding initiation and propagation structurally as well as energetically. The effect of N-terminal diproline and charged side chains is assessed on the stabilization of helical conformation in alanine-based short peptides using circular dichroism (CD) with water and methanol as solvent. A1 (Ac-Pro-Pro-Ala-Lys-Ala-Lys-Ala-Lys-Ala-NH2 ) is designed to assess the effect of N-terminal homochiral diproline and lysine side chains to induce helical conformation. A2 (Ac-Pro-Pro-Glu-Glu-Ala-Ala-Lys-Lys-Ala-NH2 ) and A3 (Ac-dPro-Pro-Glu-Glu-Ala-Ala-Lys-Lys-Ala-NH2 ) with N-terminal homochiral and heterochiral diproline, respectively, are designed to assess the effect of Glu...Lys (i, i+4) salt bridge interactions on the stabilization of helical conformation. The CD spectra of A1, A2 and A3 in water manifest different amplitudes of the observed polyproline II (PPII) signals, which indicate different conformational distributions of the polypeptide structure. The strong effect of solvent substitution from water to methanol is observed for the peptides, and CD spectra in methanol evidence A2 and A3 as helical folds. Temperature-dependent CD spectra of A1 and A2 in water depict an isodichroic point reflecting coexistence of two conformations, PPII and β-strand conformation, which is consistent with the previous studies. The results illuminate the effect of N-terminal diproline and charged side chains in dictating the preferences for extended-β, semi-extended PPII and helical conformation in alanine-based short peptides. The results of the present study will enhance our understanding on stabilization of helical conformation in short peptides and hence aid in the design of novel peptides with helical structures. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Examination of the Effect of N‐terminal Diproline and Charged Side Chains on the Stabilization of Helical Conformation in Alanine–based Short Peptides: A Molecular Dynamics Study

AbstractThe effect of N‐terminal diproline segment and charged side chains on the stabilization of helical conformation in alanine‐based short peptides are examined using molecular dynamics (MD) simulations. The cationic peptides, Ac–Pro1–Pro2–Ala3–Lys4–Ala5–Lys6–Ala7–Lys8–Ala9–NH2 (Ia) and Ac–DPro1–Pro2–Ala3–Lys4–Ala5–Lys6–Ala7–Lys8–Ala9–NH2 (IIa) are examined for the role of lysine side chains on the inducement of helical conformation in alanine‐based short peptides. To examine the influence of lysine and glutamic acid in the i, i + 4 arrangement on the stabilization of helical conformation, cationic peptides, Ia and IIa, are modified as ion‐pair peptides, Ac–Pro1–Pro2–Glu3–Glu4–Ala5–Ala6–Lys7–Lys8–Ala9–NH2 (Ib) and Ac–DPro1–Pro2–Glu3–Glu4–Ala5–Ala6–Lys7–Lys8–Ala9–NH2 (IIb), respectively. MD simulations manifest enhanced occupancies in the α basin of ϕ, ψ space for ion‐pair peptides as compare to cationic peptides. The radial distribution function (RDF) analysis highlight that large side chain substituents of lysine and glutamic acid assist in helix formation by blocking water molecules from solvating backbone CO and NH groups.

Copolymerization of chiral propargylethers and N-propargylamide and conformational control of the copolymers

The novel acetylene monomers, L-proline-derived chiral propargylether (PA, PC, PL, and PM) were synthesized. The copolymerization of L-proline-based propargylether having amide group (PR) with N-(tert-butoxycarbonyl)-L-alanine-N-propargylamide (LA) by different unit ratio and the control of conformation of poly(LA-co-PR) were discussed. The copolymerization catalyzed by (nbd)Rh+[η 6-C6H5B−(C6H5)3] afforded copolymers with medium M n. The specific rotation of poly(LA88-co-PA12), poly(LA88-co-PC12), and poly(LA88-co-PL12) was 250°, 967°, and 1117°, respectively. The specific rotation of poly(LA-co-PC) ranged from −967° to −167°. Conformation change of poly(LA88-co-PR12) and poly(LA-co-PC) in different solvents was studied and it was found that the intramolecular hydrogen bonding in the side chain significantly contribute to the stabilization of helical conformation of the copolymers and that solvent polarity strongly affected the stability of helical conformation. The helical structure of poly(LA88-co-PL12) was affected by temperature change.

ChemInform Abstract: Heterogeneity and Stability of Helical Conformations in Peptides: Crystallographic and NMR Studies of a Model Heptapeptide.

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Heterogeneity and Stability of Helical Conformations in Peptides: Crystallographic and NMR Studies of a Model Heptapeptide

The helix is a common secondary structural element in proteins. Several subtypes of helical structures are possible, depending on the nature of the backbone hydrogen-bonding pattern. For short peptides in solution, more than one helical conformation may be in equilibrium. Most of the time it is extremely difficult to identify experimentally the interconversion between different helix forms in solution, although one of the helical structures may be trapped in single crystals. This report analyzes crystallographic and NMR studies of a model heptapeptide, Boc-Leu-Aib-Val-Ala-Leu-Aib-Val-OMe, designed to probe conformational heterogeneity and relative stability of different helical structures. In crystals the peptide adopts a right-handed 310-helical structure, terminated by a left-handed helical conformation (αL) at Aib(6) resulting in a 6→1 hydrogen bond at the C-terminus. The crystals are in space group P21, a = 9.843(4) Å, b = 19.944(4) Å, c = 12.456(2) Å, β = 102.51(2)°, Z = 2, R = 10.1%, and Rw = 9.21% for 2301 reflections; |F| > 3σ(F). In CDCl3 NMR studies establish that the NH groups of residues 3−6 are hydrogen bonded, consistent with a continuous 310-helix or the conformation observed in crystals. In (CD3)2SO, NMR studies reveal that the NH groups of residues 1−3 are solvent exposed, supporting an α-helical structure. However, NMR data suggest appreciable conformational heterogeneity in solution, with population of extended states and conformations resembling the structure in crystals. Helical conformations terminated by αL residues may be an important subset of helical structure in peptides, particularly when the penultimate residue is achiral or has a propensity to adopt αL conformations.

Stability of helical conformation and reactivity of optically active poly(triphenylmethyl methacrylate) in solution

AbstractThe stability of the helical conformation in optically active poly(triphenylmethyl methacrylate) (PTrMA) was investigated by heating the polymer solutions at 100°C. The optical rotation slowly disappeared with time, and some preliminary experiments showed that this phenomenon is not due to a typical racemization process, as it is accompanied by a loss of triphenylmethyl (Tr) groups due to secondary reaction. Experimental results in the presence of methanol indicated that the decrease of optical activity occurs according to first‐order kinetics and qualitatively methyl triphenylmethyl ether was isolated from the final solution. In order to explain the above results, full characterization of copolymers obtained by interrupting the methanolysis at different conversions was performed. As a working hypothesis, it was assumed that the reaction starts at the end of the helices with a Tr‐oxygen bond fission and the reaction proceeds along the chain mainly with formation of block copolymers consisting of one block of PTrMA and one block of a probably random methacrylic acid anhydride/methacrylic acid copolymer.

Effect of sequence‐specific interactions on the stability of helical conformations in polypeptides

AbstractA modification of the Zimm–Bragg two‐state model for the helix–coil transition in polypeptides, which considers the effect of charge–dipole, charge–charge, and other specific interactions on helix stability, is presented. The new model introduces a series of adjustable parameters whose values are estimated by fitting to recent spectroscopic results on medium‐sized peptides. This formalism, based on traditional two‐state helix–coil transition models, provides a framework in which data on the helix contents of peptides of specific sequence can be rationalized by a statistical mechanical theory.

Stability of helical conformations of polyoxymethylene

Stability of helical conformations of polyoxymethylene

On the calculation of molecular conformation in crystalline polymers

The stability of helical conformations in simple polymer chains should depend upon intramolecular interactions, which can be described in a first approximation in terms of repulsive forces between nonbonded atoms along the chain plus a small contribution from dispersion forces. Using the same consistent set of interaction parameters as in a previous work on small molecules, the conformational potential energy of isolated polymer chains satisfying the postulate of the conformational equivalence of each monomeric unit has been investigated as a continuous function of skeletal bond angles. The most stable conformations corresponding to the deepest minima of the potential energy plot for polyethylene, polytetrafluoroethylene, polyoxymethylene and polyethylene oxide are in good agreement with the conformations experimentally observed from X-ray diffraction patterns.