Polypeptide random coil

Gel permeation chromatography of protein linear random coils in guanidinium chloride allows simultaneous resolution and molecular weight analysis of polypeptide components. Column calibration results are expressed in terms of a log M vs. Kd plot or of effective hydrodynamic radius (Re/). For linear polypeptide random coils in 6M GuHCl, Re is proportional to M0 555, and M° 555 or Re may be used interchangeably. Similarly, calibration data may be interpreted in terms of N° 555 (N is the number of amino acid residues in the polypeptide chain), probably the most appropriate calibration term provided sequence data are available for standards. Re for randomly coiled peptide heteropolymers is insensitive to amino acid residue side-chain composition, permitting incorporation of chromophoric, radioactive, and fluorescent substituents to enhance detection sensitivity. 

Kim KT, Park C, Vandermeulen GWM, Rider DA, Kim C, Winnik MA, Manners I (2005) Gelation of helical polypeptide-random coil diblock copolymers by a nanoribbon mechanism. Angew Chem Int Ed 44 7%4-7968... 

Kuo S-W, Lee H-F, Huang C-F, Huang C-J, Chang F-C (2008) Synthesis and self-assembly of helical polypeptide-random coil amphiphilic diblock copolymer. J Polym Sci A Polym Chem 46 3108-3119... 

The basic features of folding can be understood in tenns of two fundamental equilibrium temperatures that detennine tire phases of tire system [7]. At sufficiently high temperatures (JcT greater tlian all tire attractive interactions) tire shape of tire polypeptide chain can be described as a random coil and hence its behaviour is tire same as a self-avoiding walk. As tire temperature is lowered one expects a transition at7 = Tq to a compact phase. This transition is very much in tire spirit of tire collapse transition familiar in tire theory of homopolymers [10]. The number of compact... 

Resilin-like polypeptide and sequence motif Technique Helices (%) Strands (%) Turns (%) Unordered (%) (or random coil) Beta sheet (%) PPII (%)... 

Historically, after the development of oligopeptide-based vesicles, several groups developed and characterized vesicles using polypeptide hybrid systems consisting of polypeptide and synthetic polymer blocks [17-19]. Soon thereafter, vesicles formed entirely from polypeptides, such as poly(L-lysine)-h-poly(L-leucine) and poly(L-lysine)-h-poly(L-glutamate), were developed [20, 21]. This review will focus on recent developments in the formation of vesicles composed of polypeptide hybrid or polypeptide systems, as well as the potential promise of these systems as effective dmg delivery vehicles. A specific example of a polypeptide-based vesicle is shown in Fig. 1, where the hydrophobic segment is a-helical and the hydrophilic segment is a random coil. 

Fig. 1 Vesicle construct formed from poly(L-lysine)-i)-poly(L-leucme) polypeptides where the poly(L-leucine) block corresponds to the a-helical hydrophobic segments and the poly (L-lysine) block corresponds to the random coil hydrophilic segments. Note that this is one specific example and not all vesicle constructs have a-helical and random coil blocks. Moreover, the amphiphilic copolymer can be comprised of either a pure block copolypeptide or a macromolecule consisting of a polypeptide and another type of polymer. Adapted from [20] with permission. Copyright 2010 American Chemical Society...

For years, the reigning paradigm for the unfolded state has been the random coil, whose properties are given by statistical descriptors appropriate to a freely jointed chain. Is this the most useful description of the unfolded population for polypeptide length scales of biological interest The answer given by this volume is clear there is more to learn. But first a word about the occasion that prompted this volume. 

Fig. 2. Comparison of amide 1 + II IR absorption (left) and VCD (right) spectra of polypeptides dissolved in H2O obtained for a-helical poly-(LKKL) in high salt (top), /3-sheet poly-(LK) with high salt (middle amide F measured only in D2O), and random coil poly-K at pH 7 (bottom), where L is L-Leu and K is L-Lys. All spectra were rescaled to have an amide I absorbance maximum of A = 1.0, but are offset to avoid overlap. 

Before discussing details of their model and others, it is useful to review the two main techniques used to infer the characteristics of chain conformation in unordered polypeptides. One line of evidence came from hydrodynamic experiments—viscosity and sedimentation—from which a statistical end-to-end distance could be estimated and compared with values derived from calculations on polymer chain models (Flory, 1969). The second is based on spectroscopic experiments, in particular CD spectroscopy, from which information is obtained about the local chain conformation rather than global properties such as those derived from hydrodynamics. It is entirely possible for a polypeptide chain to adopt some particular local structure while retaining characteristics of random coils derived from hydrodynamic measurements this was pointed out by Krimm and Tiffany (1974). In support of their proposal, Tiffany and Krimm noted the following points ... 

Tanford (1968) reviewed early studies of protein denaturation and concluded that high concentrations of Gdm-HCl and, in some cases, urea are capable of unfolding proteins that lack disulfide cross-links to random coils. This conclusion was largely based on intrinsic viscosity data, but optical rotation and optical rotatory dispersion (ORD) [reviewed by Urnes and Doty (1961) ] were also cited as providing supporting evidence. By these same lines of evidence, heat- and acid-unfolded proteins were held to be less completely unfolded, with some residual secondary and tertiary structure. As noted in Section II, a polypeptide chain can behave hydrodynamically as random coil and yet possess local order. Similarly, the optical rotation and ORD criteria used for a random coil by Tanford and others are not capable of excluding local order in largely unfolded polypeptides and proteins. The ability to measure the ORD, and especially the CD spectra, of unfolded polypeptides and proteins in the far UV provides much more incisive information about the conformation of proteins, folded and unfolded. The CD spectra of many unfolded proteins have been reported, but there have been few systematic studies. 

Fig. 6. Global structural characterization of mPrP(23-231). Dots represent the 98 residues of the N-terminal segment 23-120, which shows features of a flexible, random coil-like polypeptide with rotational correlation times for the groups of Tc

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