Coil conformations, polypeptide

Polypeptides and poly(a-amino acid)s have a quite unique position amongst synthetic polymers. The reason for this is that most common synthetic polymers have very little long range order in solution and their properties are the products of statistical random coil conformations. Polypeptides, in contrast, can adopt well defined, ordered structures typical of those existing in proteins, such as a-helix and P-struc-tures. Moreover, the ordered structures can undergo conformational changes to the random coil state as cooperative transitions, analogous to the denaturation of proteins. 

Figure 2 Typical VCD and FUR Solution-Phase Spectra of Helix, Sheet, and Coil Conformations for Polypeptides (A) Alternate LKKL, (B) Alternate LK (high salt), and (C) Poly-L-Lys (neutral pH),230 a...

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. 

Fig. 27. Characteristic ratios 0/(A7p) plotted against molar weight of monomeric residue for polypeptides in random-coil conformation...

Effect of pH on the Conformation of a-Helical Secondary Structures The unfolding of the a helix of a polypeptide to a randomly coiled conformation is accompanied by a large decrease in a property called its specific rotation, a measure of a solution s capacity to rotate plane-polarized light. Polyglutamate, a polypeptide made up of only l-G1u residues,... 

Approximately one half of an average globular protein is organized into repetitive structures, such as the a-helix and/or 3-sheet. The remainder of the polypeptide chain is described as having a loop or coil conformation. These nonrepetitive secondary structures are not... 

In fact, for random-coil conformations, b in Equation 41 is explicitly related to the exponent in the Mark-Houwink equation by 3b = a 1. In this way values of M may be determined directly from measurements of D° provided KD and b are known. Although both these parameters could in principle be calculated from a detailed knowledge of the geometry of the solute, it is usual to regard them as experimentally determinable parameters. A similar relationship has also been found to hold true for the polypeptide poly(y-benzyl L-glutamate) (PBLG) dissolved both in 1,2-dichloroethane and in dichloroacetic acid. These results are shown in Figures 6 and 7, respectively. 

The mechanism of the photoresponse was tentatively explained as follows. When azo units are in the planar, apolar, trans configuration, they merge into the hydrophobic core of the micelles, forcing the polypeptide chains to assume a coil conformation. Isomerization of the azo units to the skewed, polar, ds configuration inhibits hydrophobic interactions and causes the azo units to retreat from of the micelles, thus allowing the polypeptide chains to adopt the a-helix structure favored in the absence of micelles. In other words, the primary photochemical event is the trans-ds isomerization of the azobenzene... 

The structures of spiropyran-modified poly(L-glutamate)s are strongly affected by light or dark conditions, as demonstrated by the CD spectra in Figure 10. Before irradiation, the colored solutions show the CD spectrum of a random coil conformation. After exposure to sunlight, the colorless solutions display the typical CD pattern of the a-helix, thus indicating that the isomerization of the side chains causes a transition from coil to helix in the polypeptide chains. The photoinduced conforma-... 

Blackwell and his co-workers have used circular dichroism spectroscopy to study the interactions of glycosaminoglycans with collagen, and with synthetic cationic polypeptides. In the absence of glycosaminoglycans, poly-L-lysine and poly-L-arginine exist in an extended charged coil conformation. Glycosaminoglycans bind to these cationic polypeptides and cause them to assume an a-helical conformation. In a series of systematic studies (76-83). Blackwell and his co-workers... 

Fig. 2. Temperature dependence of the partial specific heat capacity for pancreatic ribonuclease A (RNase), hen egg-white lysozyme (Lys), sperm whale myoglobin (Mb), and catalase from Thermus thermophilus (CTT). The flattened curves are for RNase and Lys with disrupted disulfide cross-links and for apomyoglobin, when polypeptide chains have a random coil conformation without noticeable residual structure (Privalov et al., 1988).

Calculations of end-to-end distances of random coil conformations have also been carried out for polypeptide copolymers (Miller et al., 1967). The values of (rzyQlnplz were found to vary markedly with composition and amino acid sequence in the copolymers. For example, the introduction of glycine residues randomly into poly-L-alanine led to a monotonic decrease 6 ... 

The study of the raesophases by X-ray diffraction, electron microscopy, infrared spectroscopy and circular dichroism20-2S has shown that the structure is always lamellar and can be described as follows the lamellar structure consists of plane, parallel, and equidistant sheets of thickness d each sheet results from the superposition of two layers one of thickness dA formed by the polyvinyl chains in a more or less random coil conformation, the other with a thickness dB formed by the polypeptide chains in an a helix conformation, oriented perpendicular to the plane of the layers, arranged in a bidimensional hexagonal array, and generally folded. 

The major casein monomer subunits have random coil conformation that facilitates strong protein-protein interaction via hydrophobic and ionic bonding. The unique amphiphilic structure, which arises from separately clustered hydrophobic and negatively charged (acidic and ester phosphate) amino acid residues along the polypeptide chain, makes them susceptible to pH and Ca ion concentration effects. This amphiphilic nature is probably responsible for the excellent surfactant properties of commercial caseinate in a variety of food applications. 

Two attempts have been reported to predict the conformation of a polypeptide hormone by assembling the appropriate residues in their predicted conformation (63, 90). In this manner, the amino acid sequence of bradykinin was predicted to exist in a random coil conformation, with variation around the glycine bond, and with no interaction predicted between phenyl groups. As yet no experimental evidence confirms this prediction however, existing experimental evidence suggests that the prediction is reasonable (67-69). In the second study the conformation of gastrin tetrapeptide was predicted (90). 

It is clear from this discussion that the measurement of volume changes which accompany titration of proteins and of model compounds represents a potentially fruitful area of research. It would be of special interest to have available AF values for synthetic polypeptides (or for naturally occurring substances such as a-corticotropin), which exist in aqueous solutions in a randomly coiled conformation. 

The behaviour of copolymers SK Is typical for the behaviour of copolymers with a hydrophobic polyvinyl block and a hydrophilic polypeptide block. They exhibit mesophases in water for water concentration ranging from 0 to 50% and the structure of the mesophases is lamellar The special feature of this lamellar structure consists in the conformation of the polylysine chains which are roughly to 15% in a P-chain conformation, to 35% in an a-helix conformation and to 50% in a coiled conformation so that the hydrophilic block of such amphipatic copolymers has the same type of conformation as the hydrophilic part of the membrane proteins. 

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