Lysine polypeptide helical content

The aim of this final section is twofold. It will first examine the basis upon which the rotatory dispersions of proteins may be treated in the same manner that has been employed for synthetic polypeptides and, secondly, assess the extent to which the dispersive properties of proteins may be quantitatively explained in terms of known conformations of a polypeptide chain. A pattern of conformational analysis embodying the hypothesis that a polypeptide chain is partitioned into standard helical segments and disordered regions has been shown capable of a rather precise estimate of partial helical content in polymers such as poly-L-lysine and copoly-L-... 

If water replaces dichloroacetic acid or trifluoroacetic acid as the hydrogen-bonding component in mixtures of decreasing polarity, then the helical content of disordered water-soluble polypeptide chains will increase continuously, as is, for example, the case with equimolar copoly-L-lysine-L-... 

What accommodations, then, must be made in the pattern of analysis developed for standard synthetic polypeptides if it is to yield quantitative estimates of partial helical content in proteins The requirements are much the same as those set out for poly-L-lysine (see Section III, G, 3), yet since globular proteins, like copolymers of L-lysine and L-glutamic acid, cannot be made completely helical in aqueous solution, a helical reference conformation must be taken either from other standard molecules or from the nonaqueous behavior of the protein in question. This latter procedure involves solvent changes with little bearing on native conditions and may be impossible to carry out in the face of restraints imposed by proline and cross-links, so that standard helical dispersion can more feasibly serve as this reference conformation. 

A value of be = —630 is well established for synthetic polypeptides and fibrous proteins. The considerations leading to the reasonable approximation that be of the disordered chain is zero, together with the implied equality of Xo and for this state, have been discussed in Section III, C, 1, and incorporated into the pattern of analysis for partial helical content as set out in Section III, G, 2. A value of ao = 4-650 has been obtained for poly-L-glutamic acid, poly-L-lysine, and Pinna nobilis tropomyosin under the appropriate conditions. As has been stressed, these constants have conformational significance only when a value of 212 nm is used for Xo. 

The catalytic efficiency was at least partially due to the depression of lysine pfC values caused by the presence of neighboring protonated lysines in the folded helix, and the resulting increased propensity for imine formation. Although the peptide was partially disordered there appeared to be a correlation between helical content and catalysis and specific acid catalysis was an important feature of the reaction mechanism. Follow up publications by Allemarm in ordered polypeptide scaffolds showed enhanced activity [25]. 

From Fig. 95 it can be seen that [a]x, say at 500 m/i, is more negative for the randomly coiled configurations than for the helical ones. On the basis of similar observations on a variety of polypeptides, it appears possible to generalize and state that the conversion of the helix to the random coil is accompanied by a decrease in [a]x. This is illustrated in Table XVII for a series of copolymers of L-glutamic acid and L-lysine in water solution, the per cent helix depending on the composition. If one wishes to obtain a very crude estimate of helical content from [ajx, one can assign some value such as 90° to 100° as the difference between the helix and random coil (on the basis of observations such as those indicated in Fig, 95 for PBG) and then express the per cent helical content in terms of the ratio of the observed value of [a]x to the assumed total change of 90° or 100°. 

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