Helix formation in peptides

Peptide models of a-helices have revealed much about the intrinsic and extrinsic factors that control helix formation in peptides and proteins (1-5). While considerable progress has been made in our understanding of helix formation and stabilization, the same cannot be said of the situation regarding two other important classes of secondary structure p-sheets and p-tums. The reason for this is that there has not yet been a p-sheet model developed that is as simple to prepare and as easy to characterize as a monomeric helix. 

Case, E. H., J. Brennan, A. Chaka, K. D. Dobbs, D. G. Eriend, D. Frurip, P. A. Gordon, J. Moore, R. D. Mountain, J. Olson, R. B. Ross, M. Sehiller, and V. K. Shen. 2007. The third industrial fluid properties simulation challenge. Eluid Phase Equilibria. 260, 153. Celinski, S. A. and J. M. Scholtz. 2002. Osmolyte effects on helix formation in peptides and the stability of eoiled-coils. Protein Science. 11, 2048. 

Fig. 2.16 Effect of electrostatic interactions on 3i4-helix formation in an aqueous environment [1 75 a, 175 b, 176]. y -Peptides 86 and 87 adopt a stable helical conformation mediated by salt bridges near neutral pH. While the propensity of these peptides to adopt a helical conformation is strongly de-...

If Pn is the dominant conformation for oligo (Ala), the traditional description of helix formation in Ala-rich model peptides as a helix-to-coil transition may be a misnomer. Questions that remain to be addressed include the following Where does the energetic barrier come... 

Thus we find that a smaller a induces cooperation of peptide units to create a longer helical sequence, provided the environmental conditions are in favor of helix formation. This is the reason why a is often called the cooperativity parameter for the formation of helical sequences, or a polypeptide with a smaller a is referred to as more cooperative. It is crucial to understand that helix formation in polypeptides is a cooperative phenomenon. 

The presence of bulky, (3-branched side chains can be helix promoting or destabilizing depending on the environment. 100 The role of hydrophobic residues in helix stabilization has been studied in Ala-based peptides 106 as well as through Monte Carlo calculations. 107 The positioning of hydrophobic residues is also important. In amphiphilic helices, hydrophobic residues repeat approximately every three to four residues, such that one side of the helix is hydrophilic and one side hydrophobic. The amphiphilicity makes the peptide susceptible to helix formation in the presence of lipid-water interfaces. 108 109 ... 

Wang, X Espinosa, J. F., and Gellman, S. H. (2000) 12-Helix formation in aqueous solution with short ft-peptides containing pyrrolidine-based residues. J. Am. Chem. Soc. 122,4821 1822. 

Chou-Fasman parameters (Chou and Fasman, 1978) were identical for each of these peptides, as were the Zimm-Bragg s values (Scheraga, 1978) for helix formation. The peptides differ only in their hydrophobic periodicities (3.5 for peptides 1 and 2 2.0 for peptide 3) and chain lengths, thus allowing the effect of these parameters on peptide conformation to be investigated while keeping short-range interactions approximately constant. All three of these peptides adopted random conformations in very dilute, aqueous solutions, but peptides 2 and 3 could be induced to form... 

Baldauf C, Gunther R, Hofmann HI. Helix formation in a,y- and P,y-hybrid peptides theoretical insights into mimicry of a- and P-peptides. J. Org. Chem. 2006 71 1200-1208. 

All of these synthetic signal peptides, as well as peptides resembling the signal sequences of lysozyme and lipoprotein (Reddy and Nagaraj, 1985), became partially a helical in polyfluorinated alcohols [trifluoroethanol (TFE) and hexafluoroisopropanol (HFIP)], which are more hydrophobic than water and have been used as models for the membrane interior. These solvents promote the formation of intramolecular hydrogen bonds, and consequently induce a-helix formation. In... 

Williams S, Causgrove T P, Gilmanshin R, Fang KS, Callender R H, Woodruff WH and Dyer R B 1996 Fast events in protein folding helix melting and formation in a small peptide Biochemistry ZS 691-7... 

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