Polypeptide helical property

When azobenzenes are attached to polypeptides, photochromic reactions of azobenzenes can induce the change in helical properties of the polypeptides, which may be detected by CD spectrum as well as optical rotation. For 4-phenylazophen-ylamine-condensed poly(y-glutamic acid) A-9 containing up to 80 mol% of 4-phenylazophenylamide side chain, UV irradiation in organic solvents, such as... 

In these relatively simple polypeptide systems, therefore, the experimental studies so far performed suggest at least a crude correlation between the capacity of a solvent to disrupt polypeptide helices and the capacity of a solvent to form strong hydrogen bonds, although in special cases electrostatic and lyophobic interactions also appear to be involved. There is little apparent correlation whth any other independent property of the solvents. 

Although instances of lyotropic PLCs predate studies of thermotropic PLCs, as they involved solutions of comparatively esoteric species — virus particles and helical polypeptides — studies of these liquid crystals were isolated to a few laboratories. Nevertheless, observations on these lyotropic PLCs did stimulate the first convincing theoretical rationalizations of spontaneously ordered fluid phases (see below). Much of the early experimental work was devoted to characterizing the texture of polypeptide solutions. (23) The chiral polypeptides (helical rods) generate a cholesteric structure in the solution the cholesteric pitch is strongly dependent on polymer concentration, dielectric properties of the solvent, and polymer molecular weight. Variable pitch (<1 - 100 pm) may be stabilized and locked into the solid state by (for example) evaporating the solvent in the presence of a nonvolatile plasticizer.(24)... 

Heparin has been reported to complex with a variety of basic species, including biogenic amines and drugs for reviews, see Refs. 10 and 391. For its possible relevance to the pharmacological properties of heparin and complexed species, mention is made here of complexes with histamine392,393 and anthracycline antibiotics.394 C.d. studies on the interaction of basic homopolypeptides with heparin and other glycosaminogly-cans have shown that heparin is able to induce an ordered, helical conformation in the polypeptide.395 397 Similar, and even more dramatic, effects were observed with mixed basic polypeptides, presumed to represent better models for the biologically relevant interactions with plasma proteins.368... 

The long side chains of a homopolypeptide have remarkable motional freedom about multiple bonds, while the main chain forms the secondary regular conformation such as a-helix, /1-sheet, and turn, which are rigid structures. The macroscopic properties of the rigid a-helical polypeptide, therefore, highly depends on the dynamic structure of the side chains so that a lot of studies on the side chain dynamics of the a-helical polypeptides have been carried out in the solid and solution states.12,14,29 66... 

Conformation-Dependent Properties of Synthetic Polypeptides 3. Cooperative Formation of Helical Sequences... 

From the above discussion it is clear that the average conformation of a polypeptide in solution depends on both the chain length N and the co-operativity parameter a, even if the helical fraction is fixed. In particular, it has been shown that, when compared at the same fN and N, the average number of helical sequences, gN, becomes smaller as a is lowered. Thus for fixed fN and N there exist a variety of different interrupted helical conformations, depending on the magnitude of a. Figure 4 illustrates two typical examples of such conformations. This theoretical prediction makes a study of the conformation-dependent properties of synthetic polypeptides rather inviting. 

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,... 

Quantification of ORD and CD Data. In principle ORD and CD can be used to calculate the amounts of a, / , and random conformations in protein, but in practice such estimates are subject to large errors. The Moffitt-Yang plot is probably the best estimate of percentage of a-helicity, but it is unable to distinguish between the ft and random structures. A detailed analysis of CD bands and their resultant Cotton effects, combined with infrared data, is the most promising approach even here the limits of error are large (82). Traditional estimates have been based on combinations of a-helix and random coil, and attention has been centered upon estimation of helical content. Consideration of j3 structure has been introduced more recently. The technique must be calibrated empirically with synthetic polypeptides of known conformation, and the proper choice of reference is not obvious. The /3 structure seems to be particularly variable in its rotational properties (27, 82). 

The introduction at the C- or N-terminal position of a crown ether unit has been used as a strategy to control the aggregation of poly(benzyl glutamate) derivatives 19 The incorporation of the crown unit at the C-terminal position is performed using (benzo-15-crown-5)-4-amine as initiator of the polymerization of l-G1u(OBz1)-NCA. Physical properties of such crown derivatives can be modulated by the formation of sandwich 2 1 complexes driven by the addition of specific alkali metal ions. In the reported case, the formation of K+ sandwich complex between two C-terminal benzo-15-crown-5 modified helical polypeptides induced aggregation. In a similar approach,f20 addition of Cs+ to 18-crown-6 terminated helical peptides results in the formation of supramolecular assemblies having membrane ion conductivity activities. 

Nuclease behaves like a typical globular protein in aqueous solution when examined by classic hydrodynamic methods (40) or by measurements of rotational relaxation times for the dimethylaminonaphth-alene sulfonyl derivative (48)- Its intrinsic viscosity, approximately 0.025 dl/g is also consistent with such a conformation. Measurements of its optical rotatory properties, either by estimation of the Moffitt parameter b , or the mean residue rotation at 233 nin, indicate that approximately 15-18% of the polypeptide backbone is in the -helical conformation (47, 48). A similar value is calculated from circular dichroism measurements (48). These estimations agree very closely with the amount of helix actually observed in the electron density map of nuclease, which is discussed in Chapter 7 by Cotton and Hazen, this volume, and Arnone et al. (49). One can state with some assurance, therefore, that the structure of the average molecule of nuclease in neutral, aqueous solution is at least grossly similar to that in the crystalline state. As will be discussed below, this similarity extends to the unique sensitivity to tryptic digestion of a region of the sequence in the presence of ligands (47, 48), which can easily be seen in the solid state as a rather anomalous protrusion from the body of the molecule (19, 49). 

---