Helical conformation electrostatics

Fig. 2.16 Effect of electrostatic interactions on 3i4-helix formation in an aqueous environment [1 75 a, 175 b, 176]. y -Peptides 86 and 87 adopt a stable helical conformation mediated by salt bridges near neutral pH. While the propensity of these peptides to adopt a helical conformation is strongly de-...

For PLL-T-93 and PLL-T-79, the values of [0]222 in alkaline pH region are plotted against the pH (Fig. 23). These polymers tend to exist in a helical conformation at neutral pH while poly-L-lysine exists in a random coil structure. In contrast to the latter, helicity of PLL-Ts decreases with increasing pH of the system. The decrease in helicity may be caused by the electrostatic repulsion between negatively charged thymine basses which are formed by deprotonation at N-3 in the base. The helicity of PLL-T-79 is lower at neutral pH and higher at alkaline pH than that of PLL-T-93. This can be explained by the fact that the unreacted free amino units in poly-L-lysine at neutral pH assume a random coil structure, whereas at alkaline pH they exist in a helical conformation. A similar tendency was observed in the case of PLL-U-93 and PLL-U-76. 

Furthermore, electrostatic interactions may be involved in the transformation of the unfolded protein to the highly helical conformation (Fig. 5B — C) in solvents rich in the nonaqueous component. In such solvents, the effective dielectric constant is probably small enough to induce extensive ion-pairing, thereby substantially reducing the electrostatic free energy contribution to the helical conformation below that existing in water, and making a more extensively helical conformation more favorable. 

Coates and Jordan, 1960 Herskovits et cU., 1961) suggest that the phosphate groups of the DNA molecule are extensively paired to counterions in methanol solution, such that a /D (Section IV,B,1) is only roughly one-sixth of its value in water. This applies to the disrupted conformation of the DNA molecule as it exists in methanol solutions, but it may be assumed that a /D is not greatly different for the hypothetical native helical conformation in methanol. It can be concluded, therefore, that there is a net reduction in electrostatic repidsive interactions, and in electrostatic free energy, for the native conformation of DNA in methanol compared to water. Similar considerations apply in ethanol, whose dielectric constant is still smaller than that of methanol. Therefore, electrostatic factors alone would tend to stabilize the helical conformation in these nonaqueous solvents, and in spite of this, the structure is disrupted. 

In summary, one may thus conclude from evidence provided by a variety of correlative methods that polypeptide chains assume a helical form in solution for clearly specified ranges of solvent polarity or pH. This result is in complete harmony with the structural proposal of Pauling et al. (1951) that polypeptide helices are stabilized by intramolecular hydrogen bonds, since competition for hydrogen bonds by polar solvents and electrostatic effects that influence this competition in water lead to disruption of these rodlike structures. Polypeptide helices of varying composition and different solvent requirements for helical stability appear, moreover, to have in common a specifically a-helical conformation that persists from the solid state into solution. 

Table 4.14 Structure (top) and physical properties [41] table below) of semi-fluorinated n-alkanes (60-63) and the homologous dialkyl bicyclohexyl liquid c stals 64 and 65 from which they are structurally derived. The spacefill model of 63 shows the helical conformation of the central perfluoroalkylene segment in contrast with the pentyl side-chains with their typical hydrocarbon zigzag conformation. The differences in charge distribution (red and blue denote negative and positive partial charges, respectively) are visualized by mapping of the electrostatic potential on to the electron density of 63 (B3LYP/6-31C //PM3 level of theory) [44, 50].

Several additional HR-C-based peptides have been designed to take advantage of intramolecular electrostatic interactions that stabilize a helical conformation, including CP32M (35), S29EK (36), SC34EK (37), and T-2635 (38) [137-143],... 

In some molecules intramolecular H-bonding, i.e. H-bonding within one molecule, can take place, which usually leads to the formation of helical structures. Such structures are particularly important in biopolymers e.g. the ot-helical conformation of polypeptides (fig. 3.5(a)). The hydrogen bond is a loose kind of bond that is largely electrostatic in nature and its strength lies somewhere between that of the covalent bond and the weak van der Waals attractive forces that are exerted by different neutral molecules when they come within about a molecular radius of each other. 

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