Polypeptide helix-coil transition

Teramoto, A. and Fujita, H. Conformation-dependet Properties of Synthetic Polypeptides in the Helix-Coil Transition Region. Vol. 18, pp. 65— 149. 

Lifson, S. Roig, A., Theory of helix-coil transition in polypeptides, J. Chem. Phys. 1961, 34, 1963-1974. 

Typical examples are the conversion of the neutral form of an amino acid into its zwitterionic form, the helix-coil transitions in polypeptides and polynucleotides, and other conformational changes in biopolymers. Reactions of higher molecularity in which reactants and products have different dipole moments are subject to the same effect (association of the carboxylic acids to form hydrogen-bonded dimers). Equilibrium involving ions are often more sensitive to the application of an electric field ... 

The influence of the solvent on chiroptical properties of synthetic polymers is dramatically illustrated in the case of poly (propylene oxide). Price and Osgan had already shown, in their first article, that this polymer presents optical activity of opposite sign when dissolved in CHCI3 or in benzene (78). The hypothesis of a conformational transition similar to the helix-coil transition of polypeptides was rejected because the optical activity varies linearly with the content of the two components in the mixture of solvents. Chiellini observed that the ORD curves in several solvents show a maximum around 235 nm, which should not be attributed to a Cotton effect and which was interpreted by a two-term Drude equation. He emphasized the influence of solvation on the position of the conformational equilibrium (383). In turn, Furakawa, as the result of an investigation in 35 different solvents, focused on the polarizability change of methyl and methylene groups in the polymer due to the formation of a contact complex with aromatic solvents (384). 

Conformation-Dependent Properties of Synthetic Polypeptides in the Helix-Coil Transition Region... 

Current investigations on dilute polymer solutions are still largely limited to the class of macromolecular solutes that assume randomly coiled conformation. It is therefore natural that there should be a growing interest in expanding the scope of polymer solution study to macromolecular solutes whose conformations cannot be described by the conventional random-coil model. The present paper aims at describing one of the recent studies made under such impetus. It deals with a nonrandom-coil conformation usually referred to as interrupted helix or partial helix. This conformation is a hybrid of random-coil and helix precisely, a linear alternation of randomly coiled and helical sequences of repeat units. It has become available for experimental studies through the discovery of helix-coil transition phenomena in synthetic polypeptides. 

Chapter B outlines a typical statistical-mechanical formulation of polypeptide conformations in terms of these three parameters and describes its use for the evaluation of s and tr from observed helix-coil transition curves. Then the reported values of AH and a for selected polypeptide-solvent pairs are given and their implications are briefly discussed from a molecular standpoint. Here AH denotes the transition enthalpy derived from s by a thermodynamic relation. 

Chapter C deals with molecular dimensions of interrupted helices. Typical theories for mean-square radius of gyration and mean-square end-to-end distance are reviewed. Important predictions from theory are compared with the results of recent light-scattering measurements. Complications attendant upon the analysis of light-scattering data for polypeptides in the helix-coil transition region are discussed. 

Chapter D is concerned with intrinsic viscosity and translational friction coefficient. Published data for the molecular-weight dependence of these quantities of polypeptides in helieogenic solvents and helix-breaking solvents are summarized, and the variations of these quantities during the helix-coil transition are described. 

Chapter E is devoted to the mean-square dipole moment and mean rotational relaxation time derived from dielectric dispersion measurements. Typical data, both in helieogenic solvents and in the helix-coil transition region, are presented and interpreted in terms of existing theories. At thermodynamic equilibrium, helical and randomly coiled sequences in a polypeptide chain are fluctuating from moment to moment about certain averages. These fluctuations involve local interconversions of helix and random-coil residues. Recently, it has been shown that certain mean relaxation times of such local processes can be estimated by dielectric dispersion experiment. Chapter E also discusses the underlying theory of this possibility. 

As will be seen below, the values of solvent systems are much smaller than unity (of the order of 10 2), whereas those of s vary within a very narrow region about unity when the polymer is in a helix-coil transition region. Thus, in general, AG > AG. It is important to note that AG and AG, and hence s and environmental conditions (temperature and solvent composition) as well as externally applied forces (electric, centrifugal, and so forth). 

The shortest helical sequence that can be created in an a-helix-forming polypeptide is hhh, and its statistical weight is as. Since s is of the order of unity in the helix-coil transition region, the probability that such a nucleus for the growth of a helical sequence will be produced is essentially equal to a. For this reason, a is also called the helix-initiation parameter. 

Figure 5 illustrates, with the data for poly(/J-benzyl L-aspartate) (PBLA) (22), that there are two types of thermal helix-coil transition, normal and inverse. It should be noted that for a given polypeptide the type of transition depends on the solvent in which the polymer is studied. This suggests that polymer-solvent interactions play a decisive role in the helix-coil transition phenomena of polypeptides. 

Table 1. Helix-coil transition parameters for synthetic polypeptides...

Several actual data illustrated in Section 5.a have demonstrated the unmistakable effects of polypeptide-solvent interactions on the helix-coil transition processes of polypeptides. This subsection deals with these effects from a thermodynamic point of view. 

In the limit of vanishing a, the transition becomes of all-or-none type, and /0 is given by 1 + [(N/2)(a1/a0)2 — 1], . The dashed line in Fig. 12 represents this relation. The fact that all other curves in Fig. 12 appear below this straight line implies that helix-coil transition of polypeptide proceeds, not in all-or-none fashion, but through interrupted helices if a is nonzero. 

Miller and Flory (43) also computed on the idea that, even in helicogenic solvents, actual polypeptides are at certain stages of helix-coil transition and showed that if the values of s and cr are chosen accordingly, chain-length dependence of 1/2 similar to that in Fig. 21 can be reproduced. Recently, Norisuye et al. (49) have confirmed this with the computation of in terms of Nagai s theory (5). 

This chapter summarizes important data for intrinsic viscosity and translational friction coefficient of polypeptides. The first half of the chapter discusses the data obtained in helicogenic solvents and in helix-breaking solvents. It is actually a supplement to the review article by Benoit et al. (61), in which such data published by 1967 were surveyed critically. The second half of the chapter is concerned with the helix-coil transition region. The context here is largely descriptive because of the lack of relevant theory. 

As far as we are aware, only a few experimental results are available for the translational friction coefficient of polypeptides in the helix-coil transition region, and our discussion about it cannot but be very incomplete. Figure 33, taken from the work of Okita et al. (13) on the system PHPG-aqueous methanol, shows the dependence of the reduced sedimentation coefficient [s0] on the helical fraction. Here [s0] is defined as s0ri0/( 1 — i>g0), with and Q0 being the... 

The question arises as to whether or how closely Eq. (D-8) is obeyed by non-randomly coiled macromolecules, especially, by polypeptides in the helix-coil transition region. An answer has been given by a recent work by Norisuye (S3), who measured [fj] and for two high-molecular-weight samples of PBLG... 

It is seen that

characteristic behavior suggests that the molecular shape of PBLG in the mixed solvent studied does not differ very much from swollen spheres of randomly coiled polymers at stages where the helical fraction is less than about 0.6. In this connection, it is worth recalling from Chapter C, Section 2.b that the dimensional features of a polypeptide remain close to Gaussian at such stages of helix-coil transition, provided the chain is sufficiently long. 

Since the mathematical expression for < u2) is equivalent to that for , measurements of should provide information which can be utilized to check the theory of , e.g. Eq. (C-3), for polypeptides in the helix-coil transition region. This idea, however, cannot be developed in straightforward fashion because there is no available theory to estimate of interrupted helical polypeptides from dielectric dispersion curves. Therefore, we are forced to proceed on some yet unproven assumptions, or even drastic approximations. 

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