Poly-DL-alanine

The synthetic polypeptide most completely studied in the solid state by optical rotation is poly-n-alanine, which Elliott et al. (1957b, 1958) treat as though it were an L-polypeptide with opposite helical sense in order to make straightforward comparison of the results with other studies. The 6o for the pure L-polymer is —475, and for two helical DL-copolymers, —500 and —505 extrapolated values for the meso-polypeptide lead to a fio of — 560. These compare favorably with Pasman s result of about —425 in 30% dichloroacetic acid in chloroform, a solvent in which the conformation is helical (I asman, 1961a). The [m ] values were found to be less than those obtained for solution, a result probably attributable to environmental changes, yet of meso-poly-DL-alanine is -f 70° at 578 m/u, which is... 

Fig. 1. A multichain copolymer in which L-tyrosine and L-glutamic acid residues are attached to multi-poly(DL-alanyl)-poly(L-lysine). Left Tyrosine and glutamic acid located in terminal positions. Right Tyrosine and glutamic acid positioned internally. Horizontal lines, poly(L-lysine) hatched area, poly(DL-alanine) , L-tyrosine O, L-glutamic acid. From M. Sela. ...

Wilchek [51] has described poly-DL-alanine poly-L-lysine agarose derivatives. These gels offer the advantage of introducing a hydrophilic spacer and thus reducing non-specific hydrophobic interactions with the spacer. 

AG is the free energy of activation for flow, h is Planck s constant, and A is the area per flow unit. This theory was applied to the surface viscosity of a number of proteins, measured as a function of surface pressure (MacRitchie, 1970). Plots of log tjs against II were found to be linear, enabling AG and A to be evaluated. The data, which are summarized in Table VI, show that the flow unit for all the proteins and poly-DL-alanine is a segment of approximately 6-8 amino acid residues and also that the free energy of activation for flow is similar for all... 

Crosslinking of protein monolayers by mercuric ion (MacRitchie, 1970) and silicic acid (Minones et al., 1973) has been reported. These studies are relevant to poisoning by heavy-metal ions and to silicosis, effects that seem likely to result from attack on the cell membrane proteins. Crosslinking by mercuric ion was detected by a spectacular increase in surface viscosity and a decrease in compressibility when a number of proteins (BSA, insulin, ovalbumin, and hemoglobin) were spread on 0.001 M mercuric chloride solution. Poly-DL-alanine was unaffected whereas poly-L-lysine and poly-L-glutamic acid were affected in a similar manner to the proteins, indicating that mercuric ion interacts with the ionizable carboxyl and amino groups on the protein side—chains. Silicic acid similarly caused protein monolayers... 

FIG. 6. Log r)s vs II for mixed monolayers of poly-DL-alanine and lecithin at pH 5.5. O, Polyalanine , polyalanine-lecithin 4 1 by weight A, polyalanine-lecithin 2 1 by weight. From MacRitchie (1970). 

Figure 2. Logarithm of surface viscosity as a function of surface pressure for several proteins and one polyamino acid at pH 5.5. o, poly-DL-alanine , human y-globulin o, pepsin , bovine serum albumin A, lysozyme. (Reproduced with permission from Ref. 6. Copyright 1970 Marcel Dekker).

A synthetic immunogen, poly-(L-tyrosine-L-glutamic acid)-poly-DL-alanine-poly-L-lysine has been used to raise immunoglobulin M in rabbits and cattle. The immobilized antigen has then been used in the purification of the immunoglobulin. 

The polypeptide, poly-DL-alanine, also gave exchange results (Bryan and Nielsen, 1960) similar to those obtained for the smaller peptides. The exchange reaction followed first-order kinetics, the rate constants (0.14 to 1.2 min" ) were of the same order of magnitude as for the simpler peptides and the exchange was subject to and OH" (D and OD") catalysis. The pH (pD) dependence of the exchange rate has been summarized in two approximate equations (Bryan and Nielsen, 1960)... 

Heidemann and Srinivasan (1967) have used H-D exchange to measure orderliness of collagen, gelatin, and poly-DL-alanine after treatment of these substances... 

The composition of the solvent strongly influences the HX rate, mainly by modifying the water ionization constant, K, and therefore the concentrations of OH" and HjO ions. Englander and Kallenhach [24] showed that the measured base-catalyzed chemical exchange rates of unstructured poly-DL-alanine in mixtures of aqueous-organic solvents (50% methanol and 50% dioxane) are reduced in... 

Names 2,5-Pyridine dicarboxyhc acid Glycine L-Alanine Poly-DL-alanine L-Aspartic acich Polyglycine Polyglycolide Polylactide CAS 100-26-5 56-40-6 56-41-7 56-84-8 25281-63A 25718-94-9 26124-68-5 26100-51-6... 

Early support for the role of polymer hydrophobicity came from a study (158) of the interaction of a series of nonionizable polypeptides (poly-DL-alanine and three derivatives of poly-L-glutamine) with SDS. Strongest interaction, as judged from the lowest T l value (from dye solubilization and electrical conductivity measurements) and highest ionic dissociation (a, from sodium ion activity measurements) of the complex, was obtained with the most hydrophobic member, viz., poly-DL-alanine, and vice versa. 

Fig. 108 are ignored, then the data obey simple first-order kinetics with a rate of the same order of magnitude as that found for simple peptides. Bryan and Nielsen also point out that urea has only a small effect on the exchange rate in poly-DL-alanine and that poly-n-glutamic acid exchanges very. slowly under conditions where it exists as a helix in solution. On the basis of these observations, as welt as recent infrared work (Elliott et al., 1958 Elliott, 1959), Bryan and Nielsen suggest tliat it is unlikely that a substantial fraction of poly-nn-alanine is in the a-helical form in aqueous solution between 0 and 22°C. they further point out that this question has to be reconsidered. 

The substitution of deuterium for hydrogen extends the usefulness of the infrared techniques, as indicated by the work of Lenormant (1950a,b) and Lenormant and Boistel (1950). In the case of poly-DL-alanine, already discussed in Section 4, Elliott (1954) found a shift of the NH stretching band toward lower frequency, with a frequency ratio of about 1.33, the expected ratio (Edsall and Scheinberg, 1940) on the basis of the increased mass of deuterium. The spectrum of deuterated poly-DL-alanine is consistent with the notion that the poljqieptide is in the a-helical form in aqueous solution. 

These estimates are based on values from poly-DL-alanine, and on values for the most slowly exchanging hydrogens. 

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