Peptide Studies

Fig. 2.35 y-Peptides studied by NMR and shown to adopt a 2.6,4-helical secondary structure. These include y-peptides with homochiral sequences consisting of enantio-pure y" -amino acid residues (139-142), y -amino acid residues of relative configuration... 

Among a number of peptides studied it is only the reduction of somatostatin in the temporal, parietal and frontal cortices that correlates with the severity of dementia in AzD, although corticotrophin-releasing factor is lower. Reductions in somatostatin do not generally parallel those of ChAT, its concentration being almost normal in the hippocampus and nucleus basalis, where ChAT levels are lowest and there is no evidence that it is localised in cholinergic neurons. 

Three theory papers are also included. Determinants of the Polyproline II Helix from Modeling Studies by Creamer and Campbell reexamines and extends an earlier hypothesis about Pn and its determinants. Hydration Theory for Molecular Biophysics by Paulaitis and Pratt discusses the crucial role of water in both folded and unfolded proteins. Unfolded State of Peptides by Daura et al. focuses on the unfolded state of peptides studied primarily by molecular dynamics. 

Gaspar, R., Jr., and R. Gaspar. 1983. Ab Initio Molecular Fragment Calculations with Pseudopotentials Model Peptide Studies. Int. J. Quantum Chem. 24, 767-771. 

DeMarco, M. L., and Daggett, V. (2004). From conversion to aggregation Protofibril formation of the prion protein. Proc. Natl. Acad. Sci. USA 101, 2293-2298. Diaz-Avalos, R., Long, C., Fontano, E., Balbirnie, M., Grothe, R., Eisenberg, D., and Caspar, D. L. D. (2003). Cross-beta structure of an amyloid-forming peptide studied by electron nano-crystallography. Fibre Diffract. Rev. 11, 79-86. 

Sheynis T, Sykora J, Benda A, Kolusheva S, Hof M, Jelinek R. Bilayer localization of membrane-active peptides studied in biomimetic vesicles by visible and fluorescence spectroscopies. Eur J Biochem 2003 270 4478-4487. 

In this elegant study it was concluded that for all the peptides studied the best separations were achieved in buffers of medium to high strength (0.05-0.1 M), thus allowing manipulation of EOF without moving away from the optimal pH for the running buffer. It was also concluded that acidic pH values in the range of 2.2-3.8 were best for analysis of basic and neutral peptides whereas acidic peptides were best run at around pH 7.0. 

Due to the huge number and variety of peptide studies carried out using IR techniques, it is impossible to provide a comprehensive review, particularly in this format. Thus a few selected examples will be provided to give the reader just a flavor of the types of experiments done, qualities of systems studied, and insights into structure obtained using IR techniques. 

Stabilization of a P-hairpin structure can be achieved in two ways, promoting a stable (or restricted) turn structure (as done with mimetics) or linking the two arms either chemically, or, more naturally, by hydrophobic interactions. In an approach to utilizing both methods, a D-Pro-Gly linkage was used to stabilize a left-handed turn (type I or II ) and various charged and hydrophobic residues were used to stabilize the molecule and enhance the interaction between arms. I252"254 Examples of these peptides studied in nonaqueous solution by IR, VCD and NMR spectroscopy exhibit characteristics of well-formed hairpins. 255 Alternatively, in aqueous solution, IR, VCD, and ECD results for related peptides agree with the NMR interpretation of conformations characterized as hairpins stabilized at the turn and frayed at the ends. 256 These latter results also have a qualitative match with theoretical simulations. Recently, examples of hydrophobically stabilized hairpins studied by NMR spectroscopy have avoided use of a nonnatural amino acid. 257,258 ... 

To verify functional results using synthetic peptides, antipeptide antisera were produced [14]. All antipeptide antisera were reactive with the native molecule. Interestingly, antisera titers correlated with the hydropathic index of the peptide, rather than with the predicted surface accessibility of the specific region in the 3-D configuration. Consistent with the peptide studies, antisera against the same four regions of the molecule inhibited IFN- activity while antisera to other regions did not. 

Triple-Helix, Based on Host-Guest Peptide Studies ... 

P. J. Milburn, Y. Konishi, Y. C. Meinwald, and H. A. Scheraga, J. Am. Chem. Soc., 109, 4486 (1987). Erratum ibid., 109, 8123 (1987). Chain Reversals in Model Peptides Studies of Cystine-Containing Cyclic Peptides. I. Conformational Free Energies of Cyclization of Hexapeptides of Sequence Ac-Cys-X-Pro-Gly-Y-Cys-NHMe. 

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