Stability of the polyglutamic acid .alpha. helix

Abstract

The intrinsic mixed acidity constant (pK,) of glutamic acid polymers has been determined from potentiometric titrations of poly-DL-glutamic acid in aqueous solutions of various NaCl concentrations and at two temperatures (25 and 48 "), thus making the difficult extrapolations of poly-L-glutamic acid titration curves more certain. These experiments indicate that p& is nearly independent of temperature but varies from 4.58 in 0.01 M NaCl to 4.32 in 0.40 M NaC1. Similar studies of the titration of poly-L-glutamic acid as a function of temperature and NaCl concentration give the standard Gibbs free-energy change per amino acid residue for the transition from un-ionized CY helix to un-ionized random coil (AGOIN) for each of the various conditions; AGOjN depends on temperature, but only slightly, if at all, on salt concentration. From the temperature dependence of the free energy, we find that AH"/N is 975 & 50 cal/(residue mole), and that AS"/N is 2.67 =t 0.1 cal/(residue mole deg). We find that there is no measurable effect of polymer concentration on these thermodynamic parameters and conclude that nonequilibrium aggregation is not present. It is demonstrated that, for poly-L-glutamic acid, three independent measures of helix content agree, namely ultraviolet absorption, titration, and optical rotatory dispersion. The helix content of un-ionized poly-DL-glutamic acid is estimated, from its extinction coefficient at 200 mp, to be 62%. The implications of these experiments for molecular theories of the conformation of polyamino acids in aqueous solutions are examined. It is found that assignment of the contribution of individual molecular forces (e.g., hydrogen bonding, hydrophobic bonding) to the over-all free energy of transition, whether that assignment is semiemprical or a priori, will have to be made with considerably more precision than has thus far been possible, if such theories are to be meaningful. n view of the pervasiveness of the a-helical conforma-

A New Model of Counterion Condensation in Polyelectrolyte Solutions II. Application to Potentiometric Titration of Weak Polyacids

“…calculated by eq 4 and 5 are listed with those by Manning theory 4 and experimental values obtained by Olander and Holtzer for poly(DLglutamic acid) (PDLG). 5 A marked difference can be seen between predictions by our models and Manning theory; the latter predicts a discontinuous change in pK. values at ()(=0.5.…”

“…Manning has already derived equations for pKa (=-log Ka) based on his condensation theory. 5 The predicted titration curve, pKa vs. IX, however, shows a break at the critical charge density above which the counterion condensation will take place. This discontinuity is caused by an artifact that the volume term, VP, for the condensed phase abruptly appears at the critical point * To whom correspondence should be addressed.…”

The α-helix folds on the millisecond time scale

“…The peptide could form monomeric ␣-helices, which subsequently aggregate to structures with a lower helix content. Poly(Glu) is known to aggregate slowly below pH 4.6, and our data were collected at pH 3.3 (21,22). Aggregation is unlikely, however, for the following reasons.…”

Small-angle X-ray scattering study on conformation of poly(sodium L-glutamate) in NaCl and NaF aqueous solutions

“…It is well known (Doty et al, 1957) that poly(d-or l-glutamic acid) (PGA) in added-salt aqueous solution exhibits a conformational transition [helix-to-coil (H/C) transition] between the helical-state (H-state) and the coiled-state (C-state) by changing pH of the solution and, thus, PGA has attracted great interest (Zimm & Rice, 1960;Nagasawa & Holtzer, 1964;Muroga et al, 1972;Olander & Holtzer, 1968) as a model for the phenomenon of folding or denaturation of proteins. As a result, the local structure in each of the conformational states has been well characterized.…”